Immunization Series Research Articles

Compliance with recommended immunizations in adolescents

Little is known about the completeness and timely administration of recommended standard immunizations in Germany. The goal of this study was to determine compliance with official standard immunization recommendations in adolescents attending secondary schools in the city of Erlangen, Germany. Adolescents who were attending 5th grade (at approximately 11 years of age), 8th grade (14 years), or 10th and 11th grade (16-17 years) classes at any of the 13 of 14 schools that had agreed to participate were eligible to be enrolled. While coverage for the primary series of diphtheria, tetanus and poliomyelitis immunizations was satisfactory (98%), coverage for measles-mumps-rubella immunizations (dose 1: 89-96%; dose 2: 60-76%) and hepatitis B (doses 1-3: 61%) was suboptimal. Of note, 39% of students had not received any immunization against pertussis. Completion of immunization series generally was significantly delayed. Furthermore, rates for recommended booster doses in adolescence were disappointingly low with 21% for tetanus component vaccines and <10% for the fifth dose of pertussis. Significant immunization gaps for all recommended standard immunizations in adolescents were detected. This puts individuals at risk for serious vaccine-preventable diseases, contributes to suboptimal herd immunity in the population under study leaving the potential for future epidemics, and impedes national and international targets of disease reduction or elimination.

Agonist Anti-GITR Antibody Enhances Vaccine-Induced CD8+ T-Cell Responses and Tumor Immunity

Immunization of mice with plasmids encoding xenogeneic orthologues of tumor differentiation antigens can break immune ignorance and tolerance to self and induce protective tumor immunity. We sought to improve on this strategy by combining xenogeneic DNA vaccination with an agonist anti-glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) monoclonal antibody (mAb), DTA-1, which has been shown previously both to costimulate activated effector CD4(+) and CD8(+) T cells and to inhibit the suppressive activity of CD4(+)CD25(+) regulatory T cells. We found that ligation of GITR with DTA-1 just before the second, but not the first, of 3 weekly DNA immunizations enhanced primary CD8(+) T-cell responses against the melanoma differentiation antigens gp100 and tyrosinase-related protein 2/dopachrome tautomerase and increased protection from a lethal challenge with B16 melanoma. This improved tumor immunity was associated with a modest increase in focal autoimmunity, manifested as autoimmune hypopigmentation. DTA-1 administration on this schedule also led to prolonged persistence of the antigen-specific CD8(+) T cells as well as to an enhanced recall CD8(+) T-cell response to a booster vaccination given 4 weeks after the primary immunization series. Giving the anti-GITR mAb both during primary immunization and at the time of booster vaccination increased the recall response even further. Finally, this effect on vaccine-induced CD8(+) T-cell responses was partially independent of CD4(+) T cells (both helper and regulatory), consistent with a direct costimulatory effect on the effector CD8(+) cells themselves.

Steroids in meningitis Part B: Clinical commentary

Steroids in meningitis Part B: Clinical commentary

Reduced-Antigen, Combined Diphtheria, Tetanus, and Acellular Pertussis Vaccine (Boostrix???)

Reduced-antigen, combined diphtheria, tetanus, and acellular pertactin-containing pertussis vaccine (dTpa; Boostrix) contains reduced quantities of the same toxoids/antigens found in a diphtheria, tetanus, and acellular pertussis vaccine (DTPa; Infanrix) used for the primary immunization series in children. A single dose of dTpa (Boostrix) is indicated for booster vaccination against diphtheria, tetanus, and pertussis in individuals aged >or=4 years in Europe and Canada, in individuals aged >or=10 years in Australia, and in adolescents aged 10-18 years in the US.A single booster dose of dTpa (Boostrix) was safe and highly immunogenic for all its component toxoids/antigens when administered to adults, adolescents (including those previously unvaccinated), and children aged >or=4 years in clinical trials conducted in various countries worldwide. It was also well tolerated, as was a second (repeat) dose administered to a small number of adolescents who had previously received the vaccine as a preschool booster. Vaccinees generally reported a low incidence of severe/grade 3, solicited, local and general adverse events during the 1-month postvaccination period.Current recommendations for dTpa usage vary from country to country; they include one dose only in adolescence or adulthood (e.g. Australia, Canada, France, Switzerland, and the US), one dose at preschool age and one in adolescence (Germany), and one dose in adolescence followed by regular (10-year) doses during adulthood (Austria). Available data support the use of dTpa (Boostrix) in place of the combined diphtheria, tetanus, whole-cell pertussis vaccine (DTwP) or DTPa booster dose in preschool children and/or the reduced-antigen, combined diphtheria, tetanus vaccine (Td) booster dose in adolescents, as well as in place of a regular Td booster dose in adults who have not previously received the vaccine.

Long-Term Follow-Up of Patients Treated in a Phase 2 Trial with MyVax® Personalized Immunotherapy (Recombinant Id-KLH with GM-CSF) after Chemotherapy as Initial Treatment for Follicular Non-Hodgkin's Lymphoma (NHL).

Background: The tumor-specific variable regions of the clonal immunoglobulin (idiotype or Id) expressed by malignant B cell NHL can be used as a target for active immunotherapy. MyVax® Personalized Immunotherapy is a patient-specific, recombinant Id protein conjugated to Keyhole Limpet Hemocyanin (Id-KLH) and administered with Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF). Several Phase 2 clinical trials have been conducted to determine the immunogenicity of MyVax® Personalized Immunotherapy. Patients andMethods: The patients all had previously untreated follicular lymphoma and achieved at least a partial response to either CVP chemotherapy (16 patients) or CVP + CHOP chemotherapy (5 patients) to be eligible to receive 5 series of immunizations with MyVax® Personalized Immunotherapy. Each immunization series consisted of MyVax® Personalized Immunotherapy administered SQ on Day 1 and GM-CSF alone on Days 2–4. The immunizations were administered over 24 weeks. The first 4 immunization series were administered every 4 weeks. The 5th immunization series was administered 12 weeks after the 4th immunization.Results: There were a total of 21 evaluable patients in the study. Both cellular and humoral immune anti-idiotype responses (IRs) were elicited using this treatment schedule. Thirteen of the 21 patients (62%) mounted an anti-idiotype immune response. Ten of the 21 patients mounted a humoral anti-idiotype response while 7 of 16 patients evaluated mounted a cellular anti-idiotype response. Immunizations with MyVax® Personalized Immunotherapy appear to be safe and well tolerated. Adverse events reported in this trial were mostly mild to moderate and transient in nature. Follicular Lymphoma International Prognostic Index (FLIPI) scores for these patients indicate that most of the patients were in the intermediate or high-risk categories. The median follow-up is over 5.5 years in this trial. The median time to disease progression was 37.7 months measured from the end of chemotherapy. Ten of the 21 patients in this trial remain progression free between 47 months and 71 months post chemotherapy as of their last follow-up. Four of the patients that remain in remission are in the high risk category by FLIPI score.Conclusions and Discussion: These results suggest that patients with a poorer prognosis according to their FLIPI score can achieve significant remissions following treatment with MyVax® Personalized Immunotherapy. MyVax® Personalized Immunotherapy is currently in a late-stage Phase 3 trial.

Priming with Plasmid DNAs Expressing Interleukin-12 and Simian Immunodeficiency Virus Gag Enhances the Immunogenicity and Efficacy of an Experimental AIDS Vaccine Based on Recombinant Vesicular Stomatitis Virus

Of the various approaches being developed as prophylactic HIV vaccines, those based on a heterologous plasmid DNA prime, live vector boost vaccination regimen appear especially promising in the nonhuman primate/simian-human immunodeficiency virus (SHIV) challenge model. In this study, we sought to determine whether a series of intramuscular priming immunizations with a plasmid DNA vaccine expressing SIVgag p39, in combination with plasmid expressed rhesus IL-12, could effectively enhance the immunogenicity and postchallenge efficacy of two intranasal doses of recombinant vesicular stomatitis virus (rVSV)-based vectors expressing HIV-1 env 89.6P gp160 and SIVmac239 gag p55 in rhesus macaques. In macaques receiving the combination plasmid DNA prime, rVSV boost vaccination regimen we observed significantly increased SIVgag- specific cell-mediated and humoral immune responses and significantly lower viral loads postintravenous SHIV89.6P challenge relative to macaques receiving only the rVSV vectored immunizations. In addition, the plasmid DNA prime, rVSV boost vaccination regimen also tended to increase the preservation of peripheral blood CD4+ cells and reduce the morbidity and mortality associated with SHIV89.6P infection. An analysis of immune correlates of protection after SHIV89.6P challenge revealed that the prechallenge SHIV-specific IFN-gamma ELISpot response elicited by vaccination and the ability of the host to mount a virus-specific neutralizing antibody response postchallenge correlated with postchallenge clinical outcome. The correlation between vaccine-elicited cell-mediated immune responses and an improved clinical outcome after SHIV challenge provides strong justification for the continued development of a cytokine-enhanced plasmid DNA prime, rVSV vector boost immunization regimen for the prevention of HIV infection.

Economic Considerations for Pertussis Booster Vaccination in Adolescents

Despite good acellular pertussis vaccine safety and protective efficacy, as well as high vaccination rates among young children, the incidence of pertussis in the United States has steadily increased since the 1980s. This is especially true for adolescents and adults who are susceptible because of waning immunity, which is not long lived. Other populations are at increased risk for morbidity of infection, although infants younger than 6 months of age who have not completed the primary immunization series have the greatest morbidity and mortality. Other groups who might benefit from booster immunizations include hospital workers, family contacts, and individuals with compromised health. Although older individuals generally have milder illnesses, they are often the source of infection for younger children. An adolescent/adult formulation of acellular pertussis vaccine requires a lower dose of pertussis antigens and can be combined with currently recommended diphtheria and tetanus toxoids (Tdap). These new vaccines for adolescents and adults are safe, immunogenic, and protective. Through an extensive review of the literature, the direct and indirect costs associated with pertussis and its complications are examined, cost-benefit analyses of pertussis booster vaccination are evaluated for different groups, and the economic considerations involved in implementing a pertussis booster vaccination program in adolescents are discussed. Pertussis infections cause outbreaks in schools, families, and workplaces, resulting in prolonged morbidity and significant costs for medical care, lost time, and wages. Physician visits, chest radiographs, and antibiotics comprise the majority of direct costs, and costs associated with work loss often comprise the majority of indirect costs related to pertussis illness. Adolescents and adults also transmit their infections to nonimmune children. A cost-benefit analysis evaluated the health and economic benefits of seven strategies for administering a pertussis booster. The most economical strategy is to immunize all adolescents 10-19 years of age, which may prevent 0.4-1.8 million cases of pertussis and save US 0.3-1.6 billion dollars in a decade. A tetanus and diphtheria booster (Td) is currently recommended for children 11-12 years of age. The Tdap vaccine offers an enhancement for the Td booster by providing protection against pertussis, and it will not require an additional injection or office visit. Immunizing adolescents with a pertussis booster in the form of Tdap is the most economical and easiest-to-implement strategy and should provide significant health and economic benefits.

Health Burden of Pertussis in Infants and Children

In countries with high rates of vaccination against pertussis, the incidence of this disease has decreased dramatically compared with the prevaccine era. However, pertussis still occurs in these countries, and severe morbidity and mortality are greatest among infants, particularly those who are unimmunized or incompletely immunized. Pertussis in older children and adults is perceived by many as being a mild disease, but it is a significant health burden in persons of all ages. Infants with pertussis experience the highest rates of hospitalization, complications and death. Severe complications include pneumonia, encephalopathy and meningoencephalitis. In addition, infants may experience weight loss, bronchitis, otitis media, apnea, cyanosis, inguinal hernia and rectal prolapse. It is essential to explore methods to prevent disease transmission to infants in the months before they complete their primary immunization series. The Global Pertussis Initiative was established to assess the true health burden of pertussis in infants and to suggest strategies to combat transmission and infection with Bordetella pertussis, which remains a significant public health concern.

Lymphocyte subsets in term and significantly preterm UK infants in the first year of life analysed by single platform flow cytometry

This observational study describes the ranges observed for lymphocyte subsets for significantly preterm infants (<32 weeks) in the first year of life, measured by single platform flow cytometry and compared to identically determined subsets in term infants. After ethical approval 39 term and 28 preterm infants had lymphocyte subset analysis before and after their primary immunization series. Median values with 5th and 95th percentiles of absolute counts and percentages are presented for total lymphocytes, T cells, NK cells, B cells, cytotoxic T cells, helper T cells, dual positive T cells, activated T cells, activated T helper cells (including T regulatory cells), pan memory T cells, pan naive T cells, memory helper T cells, naive helper T cells and the T helper/suppressor ratio. The lymphocyte profile of the preterm infants differed from that of the term infants.

Hepatitis B Virus Vaccine Response in Children 15–19 Years Old

ABSTRACTTo determine Hepatitis B virus vaccine response in vaccinated children 15–19 years old. Three hundred children were vaccinated after an informed consent and after tests for Hepatitis B virus (HBV) markers (HBsAg, anti-HBc and anti-HBs) during 1999–2000 in program INTERREG II of European Community (EC). All of them were negative before vaccination. The children were vaccinated by the classic (months 0, 1 and 6) schedule (XI, XII 1999—V 2000). Recombinant Hepatitis B vaccine ENGERIX™ (SmithKline Beecham Biologicals S.A.—Belgium) was given as 20 mcg intramuscular injections via the deltoid muscle. Seroconversion was defined in 280 of them on days 30 or more after the last immunization as the presence of hepatitis B surface antibody concentration >= 10 IU/L in serum samples, while concentrations of > =100 IU/L were considered to be seroprotec-tive. The serological hepatitis B surface antibody titration was carried out using a commercial ELISA kits (DiaSorin—ETI—AB—AUK—3—Italy) and DiaSorin automated system and software. After three doses of vaccine, anti HBs concentration reached levels >=10 IU/L was determined in 96.3% of children. Protective levels >= 100 IU/L was determined in 86% of them. The initial immune response to hepatitis B vaccine following the basic immunization series is an important determinant of the duration of immunity. Our data indicate that performed Hepatitis B vaccine induced good immune response of the children vaccinated, but 3.6% of them failed to produce any antibody response and 10.3% - failed to produce protective antibody levels. For the last children a booster doses of vaccine must be applicated.

Four-year follow up of hepatitis C patients vaccinated against hepatitis B virus

Patients with chronic hepatitis C have been recommended to receive vaccinations against hepatitis B. Our study aimed at evaluating the hepatitis B immunogenicity and efficacy against hepatitis B virus infection 4 years after primary immunization series in a group of patients with chronic hepatitis C. We recruited 36 out of 48 hepatitis C virus (HCV) infected individuals who were vaccinated against hepatitis B virus (20 mug of recombinant HBsAg at 0-1-6 mo schedule) in 1998. Here we measured anti-HBs titers and anti-HBc 4 years after delivery of the third dose of primary immunization series. After 4 years a total of 13/36 (36%) HCV infected patients had seroprotective titers of anti-HBs compared with 9/10 (90%) in the control group, (P<0.05). Similarly the mean concentration of anti-HBs found in hepatitis C patients was significantly lower than that found in healthy subjects (18.3 and 156.0 mIU/mL respectively (P<0.05). None of the HCV infected patients or controls became infected with HBV during the study period as confirmed by anti-HBc negativity. We demonstrated that 4 years after HBV immunizations' more than 60% of vaccinated HCV patients did not maintain seroprotective levels of anti-HBs, which might put them at risk of clinically significant breakthrough infections. Further follow-up studies are required to clarify whether memory B and T lymphocytes can provide protection in chronic hepatitis C patients in the absence or inadequate titers of anti-HBs.

Chronic Steroid and Immunosuppressant Therapy in Children

1. Abraham Gedalia, MD* 2. Avinash K. Shetty, MD† 1. *Professor of Pediatrics and Head, Division of Pediatric Rheumatology, Louisiana State University Health Sciences Center and Children’s Hospital, New Orleans, La 2. †Assistant Professor of Pediatrics, Division of Infectious Diseases, Wake Forest University School of Medicine, Winston-Salem, NC After completing this article, readers should be able to: 1. Describe the mechanism of action, list indications for therapy, and discuss the adverse effects of corticosteroid therapy in children. 2. Delineate the mechanism of action and adverse effects of other immunosuppressive agents frequently used in children. 3. Discuss the immunization recommendations for children receiving immunosuppressive therapy. Corticosteroids are the most potent, naturally occurring anti-inflammatory agents known. Despite more than 50 years of controversy regarding their clinical use, risks, and benefits, corticosteroids still play a significant role in the management of a wide variety of diseases. They have reduced the morbidity and mortality significantly in children afflicted with leukemia, asthma, rheumatic diseases, and other inflammatory disorders. In this article, we review the mechanism of action, clinical indications, and adverse effects of corticosteroids and other commonly used immunosuppressive agents in children. We also review immunization recommendations for children receiving immunosuppressive therapy. Corticosteroids have a diverse role in the human body at the physiologic level. The actions of glucocorticoids include: 1) negative feedback modulation of corticotropin-releasing factor and adrenocorticotropic hormone; 2) regulation of blood glucose and liver glycogen levels; 3) maintenance of water-electrolyte homeostasis; 4) influence on the metabolism of protein, fat, and purine; 5) maintenance of normal cardiovascular, central nervous system (CNS), and renal functions; 6) influence on circadian rhythmicity; 7) maintenance of bone and muscle work capacity; and 8) protection of the body against moderate stress. Glucocorticoids also have pharmacologic properties that are used in the treatment of rheumatic and other inflammatory diseases. Cellular receptors for cortisol are ubiquitous in cell cytoplasm, reflecting the critical role of the hormone in maintaining cell homeostasis. The type 1 glucocorticoid receptor, known as the mineralocorticoid receptor, has high affinity for aldosterone. The type 2 glucocorticoid receptor, known as the glucocorticoid receptor, exhibits strong affinity for dexamethasone. Although …

Monetary incentives in primary health care and effects on use and coverage of preventive health care interventions in rural Honduras: cluster randomised trial

Scaling-up of effective preventive interventions in child and maternal health is constrained in many developing countries by lack of demand. In Latin America, some governments have been trying to increase demand for health interventions by making direct payments to poor households contingent on them keeping up-to-date with preventive health services. We undertook a public health programme effectiveness trial in Honduras to assess this approach, contrasting it with a direct transfer of resources to local health teams. 70 municipalities were selected because they had the country's highest prevalence of malnutrition. They were allocated at random to four groups: money to households; resources to local health teams combined with a community-based nutrition intervention; both packages; and neither. Evaluation surveys of about 5600 households were undertaken at baseline and roughly 2 years later. Pregnant women and mothers of children younger than 3 years old were asked about use of health services (primary outcome) and coverage of interventions such as immunisation and growth monitoring (secondary outcome). Reports were supplemented with data from children's health cards and government service utilisation data. Analysis was by mixed effects regression, accounting for the municipality-level randomisation. The household-level intervention had a large impact (15-20 percentage points; p<0.01) on the reported coverage of antenatal care and well-child check-ups. Childhood immunisation series could thus be started more opportunely, and the coverage of growth monitoring was markedly increased (15-21 percentage points; p<0.01. Measles and tetanus toxoid immunisation were not affected. The transfer of resources to local health teams could not be implemented properly because of legal complications. Conditional payments to households increase the use and coverage of preventive health care interventions.

Childcare immunization programme — to what extent are children covered by vaccinations in Greenland?

Objectives: New vaccines in the child healthcare programme are regularly considered. When considering the introduction of the Hepatitis-B vaccine into the programme, it was asked to what extent children in Greenland were actually covered by the existing immunization series. Would introducing new vaccines make any sense if the percentage of children immunized was shown to be low? A telephone enquiry conducted in 2000 showed a tendency of very high percentage of full coverage per child (98–99 %) in small cities and settlements, as health visitors had a policy of checking up on the immunization status for each child. In big cities and Nuuk, parents alone have the responsibility of having their child immunized. The coverage was a guess of 85-95 % for infants, falling as the child grows older. Study design. Retrospective review of registration from all Greenlandic health districts. Methods. The registration included the number of immunized children in each group of age according to the childcare immunization programme. The collected data were compared to the number of children per age group in each health district. Results and conclusion. The conclusion must be taken with some reservation on the basis of several aspects of uncertainty. As a whole, the tendencies show reasonably high vaccination coverage countrywide, but variations between districts are great. A number of children probably have their vaccination postponed somewhat in relation to recommended age, but it is fairly evident that the majority of these children are dealt with later. The coverage in a few districts is lower than desired, especially concerning DiTe4 and MMR2.

Utilization of well-baby care visits provided by Taiwan's National Health Insurance Program

In April of 1995, Taiwan's National Health Insurance Program started providing each eligible child a total of six well-baby care visits. The first four are for infancy, the fifth is for the second and the third years of life, and the sixth is for the fourth year. These services are in addition to neonatal screening and a series of primary immunizations that have been publicly financed and utilized conventionally for years. The purposes of this study were to investigate the utilization level of these well-baby care visits, and explore relevant factors. The results reveal that 36% of eligible children did not use any of the first four visits, 58% did not utilize the fifth, and 82% did not use the sixth in the late 1990s. It appears that the take-up of these services is much less than satisfactory. Maternal awareness of and attitudes toward the services appeared to be the most important factors influencing utilization. These two factors not only were most influential, but also significantly contributed to disparities in utilization among different regions and types of residential districts. As a result, they should be the focus of interventions for advancing well-baby care. While these two factors are at the individual level, they are not independent from the health care system because the health care system has impacts on individual factors. Since physicians can serve as a good vehicle for teaching parents about relevant information and correct attitudes, and most physicians in Taiwan complained about the payment scheme, offering stronger incentives for physicians to promote such services might be helpful for achieving a high utilization level of well-baby care.

Race/ethnicity and gender disparities in the utilization of a school-based hepatitis B immunization initiative

Objective To determine if participation and completion rates in a school-based hepatitis B vaccination program differ based on individual demographic factors including insurance status, race, and gender. Methods From 1998 through 2001, a school-based adolescent hepatitis B immunization initiative targeted elementary schools with a high percentage of free lunch and “at risk” students and provided free hepatitis B immunization (0,1, and 4 month schedule) during school hours. Demographic data were collected regarding potential enrollees in the project. The rate of return of consent/refusal forms, participation rates, and immunization completion rates were determined. Analyses were completed using the z statistic, frequencies, and stratified Chi-square analyses. Results Families of female children (p < .0001) and those with insurance or Medicaid were more likely than those with no insurance (p < .0001) to respond by returning a consent or refusal form and were also more likely to participate in the program by receiving at least one immunization dose (p < .0001 for both analyses). Participation rates also varied by race (p < .0001) with black and Hispanic potential enrollees participating more frequently than white and Asian potential enrollees. Females among black (p = .012) and Hispanic (p < .0001) participants and participants of Asian race/ethnicity (p < .0001) were more likely to complete the vaccination series. Conclusions Even when access issues are eliminated as a potential barrier to hepatitis B immunization, gender and race disparities exist in the participation in, and completion of, the hepatitis B immunization series given in the schools. Race and gender clearly play separate and distinct roles in health care utilization, unrelated to the traditional variables of socioeconomic status often associated with access to care.

Race/ethnicity and gender disparities in the utilization of a school-based hepatitis B immunization initiative

Objective To determine if participation and completion rates in a school-based hepatitis B vaccination program differ based on individual demographic factors including insurance status, race, and gender. Methods From 1998 through 2001, a school-based adolescent hepatitis B immunization initiative targeted elementary schools with a high percentage of free lunch and “at risk” students and provided free hepatitis B immunization (0,1, and 4 month schedule) during school hours. Demographic data were collected regarding potential enrollees in the project. The rate of return of consent/refusal forms, participation rates, and immunization completion rates were determined. Analyses were completed using the z statistic, frequencies, and stratified Chi-square analyses. Results Families of female children ( p < .0001) and those with insurance or Medicaid were more likely than those with no insurance ( p < .0001) to respond by returning a consent or refusal form and were also more likely to participate in the program by receiving at least one immunization dose ( p < .0001 for both analyses). Participation rates also varied by race ( p < .0001) with black and Hispanic potential enrollees participating more frequently than white and Asian potential enrollees. Females among black ( p = .012) and Hispanic ( p < .0001) participants and participants of Asian race/ethnicity ( p < .0001) were more likely to complete the vaccination series. Conclusions Even when access issues are eliminated as a potential barrier to hepatitis B immunization, gender and race disparities exist in the participation in, and completion of, the hepatitis B immunization series given in the schools. Race and gender clearly play separate and distinct roles in health care utilization, unrelated to the traditional variables of socioeconomic status often associated with access to care.

LUM ET AL. RESPOND

Diamond correctly points out the difficulty of making comparisons between the presence of hepatitis B surface antibodies (anti-HBs) among persons reporting prior immunizations (Seattle Young Men’s Survey [YMS]) and anti-HBs seroconversion measured after a documented immunization series (the UFO Study). Recall bias and waning anti-HBs could certainly have contributed to the lower proportion (70%) of subjects with isolated anti-HBs that YMS investigators observed.1 In the UFO Study, 62% of young injection drug users (IDUs) who reported 3 prior immunizations demonstrated isolated anti-HBs. We reported anti-HBs seroconversion in 78% of young IDUs after 3 doses of a monovalent recombinant hepatitis B virus (HBV) vaccine.2 Physiological factors that may blunt the immune response include lifestyle (e.g., smoking and obesity), biological factors (e.g., male sex and older age), and the coexistence of other immune-mediated diseases.3 Among homosexual and bisexual men, HIV infection has been associated with poorer HBV vaccine responses.4 The role of hepatitis C virus (HCV) antibody status in suboptimal HBV vaccine responses is still controversial. Some studies have reported an association,5,6 while others have found none.7,8 Our observation of a lower vaccine response among anti-HCV–positive subjects occurred in a subset too small for statistical significance. However, we plan to investigate this issue further in a new trial of hepatitis vaccine adherence among young IDUs in San Francisco. We agree with Diamond that prevaccination screening of high-prevalence populations for prior infection or immunity makes sense. At the San Francisco STD Clinic, screening was cost saving when seroprevalence was greater than 22% (J. D. Klausner, MD, MPH, STD Prevention and Control Services, San Francisco Department of Public Health; written communication; September 17, 2003). Because many young IDUs and young men who have sex with men are lost to follow-up and cannot afford to pay for either blood tests or vaccines, public health providers must often decide whether to assume these costs. Some providers have chosen a catch-as-catch-can approach, administering the first vaccine dose on the day of prevaccination screening. Finally, while understanding the factors that impair vaccine responses is important, 78% effectiveness is not all that bad. Future HIV vaccine candidates may be licensed with much lower partial efficacy.9 Strategies to improve vaccine series completion among high-risk adolescents and adults arguably present the greater challenge for the prevention of HBV transmission in the United States. Those strategies are likely to be useful not just for the delivery of HBV vaccines but also for the delivery of promising HIV vaccine candidates in the future.

The safety, reactogenicity and immunogenicity of a 7-valent pneumococcal conjugate vaccine (7VPnC) concurrently administered with a combination DTaP-IPV-Hib vaccine

To evaluate immune responses, safety and reactogenicity of the concomitant use of DTaP-IPV-Hib and the newly available 7-valent pneumococcal conjugate (7VPnC) vaccines when given as the primary immunization series in early infancy.A total of 231 healthy infants were enrolled at 11 German study centers and randomized to receive either 7VPnC plus DTaP-IPV-Hib vaccines concomitantly into opposite limbs at age 2, 3, 4 and 11-15 months (7VPnC group) or DTaP-IPV-Hib vaccine at the same ages plus a 7VPnC “catch-up vaccination” at ages 6, 7, 8 and 11–15 months (Control group). Blood samples were drawn before and 4 weeks after the first three vaccine doses and 4 weeks after the fourth dose. Local and general side effects (i.e. safety) were solicited by diary cards. Immune responses were determined by ELISA except for antibodies to polioviruses (neutralization assay).Post-dose 3, a significant antibody response against all seven pneumococcal vaccine-serotypes was observed in the 7VPnC group only. Post-dose 4 geometric mean concentrations (GMCs) were similar in both groups. GMCs for other vaccine antigens were comparable between groups except for diphtheria (higher in the 7VPnC group) and pertactin (lower in the 7VPnC group), although after three vaccine doses there was a 28-fold rise in GMCs from baseline. Both vaccines were generally well-tolerated although there were minor differences in the frequency of local reactions and somewhat more fever or drowsiness in the 7VPnC group.The use of DTaP-IPV-Hib and the 7VPnC vaccine was safe, well-tolerated and immunogenic when given concomitantly at age 2, 3 and 4 months or when given separately with 7VPnC as a catch-up vaccination at age 6, 7, 8 months and as a concomitant booster immunization at age 11–15 months.

Prescreening versus empirical immunization for hepatitis A in patients with chronic liver disease: a prospective cost analysis

OBJECTIVES: There are few prospective studies estimating the prevalence of hepatitis A in chronic liver disease patients. Furthermore, there are minimal cost-comparative data as to whether or not screening for hepatitis A exposure before immunization is an effective fiscal strategy. The objectives of this study were to determine the prevalence of prior hepatitis A infection and to perform a prospective cost analysis for hepatitis A immunization in patients with chronic liver disease. METHODS: This is a prospective cohort study of 100 patients with chronic liver diseases. Patients were screened for potential risk factors for hepatitis A including history of jaundice, socioeconomic status, birth origin, and ethnic background. Each patient underwent testing for evidence of prior infection using an ELISA. Seronegative patients then went on to receive an immunization series. Cost analysis of vaccination without prescreening (universal strategy) was compared to cost analysis of prescreening and selective immunization of those without prior infection (selective strategy). RESULTS: Fifty-three patients (53%) had serological evidence of prior hepatitis A infection (95% CI = 43–63%). Of the risk factors assessed, foreign birth was associated with prior hepatitis A exposure ( p = 0.0002). Cost analysis revealed that prescreening for hepatitis A before vaccination was cost saving given the current prevalence. CONCLUSIONS: The seroprevalence of hepatitis A in those with chronic liver diseases was 53%. Cost analysis revealed that screening for hepatitis A before immunization is cost saving, and this strategy should be applied to follow current vaccination guidelines.