Serologic testing to verify the immune status of internationally adopted children against vaccine preventable diseases

Definitive immunization guidelines for internationally adopted children are lacking. We examined whether these children had serologic evidence of protection against vaccine-preventable diseases. For children with ≥3 vaccine doses, overall protection was high for diphtheria (85%), tetanus (95%), polio (93%), hepatitis B (77%), and Hib (67%). For children ≥12 months of age with ≥1 dose of measles, mumps, or rubella vaccines, 95%, 72%, and 94% were immune, respectively. Children without immunization documentation had lower immunity. Serologic testing was useful in verifying the immunization status in internationally adopted children with and without documentation of immunizations.     

Maintenance of pathogenic Th2 cells in allergic disorders

Immunological memory is an important protective mechanism that enables host organisms to respond rapidly and vigorously to pathogens that have been previously encountered. In addition to the protective function, memory CD4⁺ T helper (Th) cells play a central role in the pathogenesis of chronic inflammatory disorders, including asthma. Recently, several investigators have identified phenotypically and functionally distinct memory Th2 cell subsets that produce IL-5. These memory Th2 cell subsets play an important role in the pathology of allergic inflammation and function as memory-type “pathogenic Th2 (Tpath2) cells” both in mice and humans. We review the role of lung Tpath2 cells in the development of allergic inflammation and, in the context of recent findings, propose a mechanism by which Tpath2 cells not only survive but also continue to function at the sites where antigens were encountered. A greater understanding of the functional molecules or signaling pathways that regulate the inflammatory niche for Tpath2 cells may aid in the design of more effective treatments for chronic inflammatory disorders.     

HUMORAL IMMUNITY AGAINST HEPATITIS B,TETANUS, AND DIPHTHERIA FOLLOWING CHEMOTHERAPY FOR HEMATOLOGIC MALIGNANCIES: A Report and Review of Literature

Malignancy and its treatment are major causes of secondary immunodeficiency in childhood. The authors investigated the effects of chemotherapy on humoral immunity against hepatitis B, tetanus, and diphtheria in children with hematologic malignancies. The authors recruited 54 patients with hematologic malignancies after the completion of chemotherapy (group A), 25 patients with newly diagnosed hematologic malignancies before initiation of chemotherapy (group B), and 74 healthy controls (group C). All participants had been vaccinated against hepatitis B, tetanus, and diphtheria according to the Iranian national vaccination scheme. Patients in group A achieved protective levels of diphtheria and hepatitis B antibodies significantly less frequently than the other 2 groups and protective levels of tetanus antibody significantly less frequently than group C (P <.05). After controlling for age, the association observed for tetanus lost its significance, but chemotherapy was a significant and independent predictor of failure to achieve protective levels of antibodies against diphtheria (odds ratio [OR] = 7.7, P < .001) and hepatitis B (OR = 3.13, P = .008). These results indicate that chemotherapy has independent adverse effects on vaccine-induced antibody protection against diphtheria and hepatitis B.     

U.S. Postlicensure safety surveillance for adolescent and adult tetanus,diphtheria and acellular pertussis vaccines: 2005–2007

Background

Pre-licensure clinical trials for two U.S. licensed tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines did not reveal any major safety concerns. However, routine use in large adolescent and adult populations could reveal rare and potentially serious adverse events (AEs).

Methods

To characterize reported AEs following Tdap vaccination and identify potential safety concerns warranting further evaluation, we analyzed data from the Vaccine Adverse Event Reporting System (VAERS) and assessed the frequency and proportions of AEs and reporting rates (reports per 100,000 vaccine doses distributed).

Results

A total of 2090 reports (7% were serious; 55% listed Tdap alone) involving Tdap vaccines were submitted to VAERS May 2005–June 2007. The crude reporting rate was 10.2 per 100,000 vaccine doses distributed. The median age of vaccinees was 22 years, and the female to male ratio was about 2 to 1. The majority of reports described common local and systemic signs and symptoms, such as injection site reactions, fever, and headache. Rarely reported AEs included myopericarditis, demyelinating diseases of the central nervous system, Guillain–Barré Syndrome, syncope, encephalopathy/encephalitis, seizure, Bell's palsy, anaphylaxis, and thrombocytopenia.

Conclusions

Because adolescents and adults were not routinely vaccinated against pertussis in the past, this surveillance summary provides important – and reassuring – information about the use of Tdap in these age groups. Although subject to the limitations of passive surveillance, the findings of this VAERS review support the pre-licensure clinical trial data with regard to the safety of the U.S. licensed Tdap vaccines. Continued monitoring of clinically significant AEs that are temporally associated with Tdap vaccination and further assessment of such events using controlled observational studies may provide additional information about the safety of these vaccines.     

Systematic review of reporting rates of adverse events following immunization: An international comparison of post-marketing surveillance programs with reference to China

Background

China is the most populous country in the world, with an annual birth cohort of approximately 16 million, requiring an average of 500 million vaccine doses administered annually. In China, over 30 domestic and less than 10 overseas vaccine manufacturers supply over 60 licensed vaccine products, representing a growing vaccine market mainly due to recent additions to the national immunization schedule, but data on post-marketing surveillance for adverse events following immunization (AEFI) are sparse.

Objectives

To compare reporting rates for various categories of AEFI from China with other routine post-marketing surveillance programs internationally.

Methods

Systematic review of published studies reporting rates of AEFI by vaccine, category of reaction and age from post-marketing surveillance systems in English and Chinese languages.

Results

Overall AEFI reporting rates (all vaccines, all ages) in Chinese studies were consistent with those from similar international studies elsewhere, but there was substantial heterogeneity in regional reporting rates in China (range 2.3–37.8/100,000 doses). The highest AEFI reporting rates were for diphtheria–tetanus–pertussis whole-cell (DTwP) and acellular (DTaP) vaccines (range 3.3–181.1/100,000 doses for DTwP; range 3.5–92.6/100,000 doses for DTaP), with higher median rates for DTwP than DTaP, and higher than expected rates for DTaP vaccine. Similar higher rates for DTwP and DTaP containing vaccines, and relatively lower rates for vaccines against hepatitis B virus, poliovirus, and Japanese encephalitis virus were found in China and elsewhere in the world.

Conclusions

Overall AEFI reporting rates in China were consistent with similar post-marketing surveillance systems in other countries. Sources of regional heterogeneity in AEFI reporting rates, and their relationships to differing vaccine manufacturers versus differing surveillance practices, require further exploration.     

肺结核可疑症状者求医行为模式及影响因素

我国是全球22个结核病高负担国家之一^[1].提高患者发现率是我国控制结核病的重点和难点,而肺结核可疑症状者的求医行为模式是决定发现率的关键因素.国外对肺结核可疑症状者求医行为模式的研究多是以社区为基础,而我国的研究则多以医院为基础,鲜见针对社区人群的研究^[2,3],其结论难以代表社区中全部可疑症状者.为此本文综述肺结核可疑症状者的求医行为及影响因素,为改善求医行为模式,提高我国结核病患者发现率提供参考依据.     

Genetic variants within the MHC region are associated with immune responsiveness to childhood vaccinations

The influence of genetic variability within the major histocompatibility complex (MHC) region on variations in immune responses to childhood vaccination was investigated. The study group consisted of 135 healthy infants who had been immunized with hepatitis B (HBV), 7-valent pneumococcal conjugate (PCV7), and diphtheria, tetanus, acellular pertussis (DTaP) vaccines according to standard childhood immunization schedules. Genotype analysis was performed on genomic DNA using Illumina Goldengate MHC panels (Mapping and Exon Centric). At the 1 year post vaccination check-up total, isotypic, and antigen-specific serum antibody levels were measured using multiplex immunoassays. A number of single nucleotide polymorphisms (SNPs) within MHC Class I and II genes were found to be associated with variations in the vaccine specific antibody responses and serum levels of immunoglobulins (IgG, IgM) and IgG isotypes (IgG1, IgG4) (all at p < 0.001). Linkage disequilibrium patterns and functional annotations showed that significant SNPs were strongly correlated with other functional regulatory SNPs. These SNPs were found to regulate the expression of a group of genes involved in antigen processing and presentation including HLA-A, HLA-C, HLA-G, HLA-H, HLA-DRA, HLA-DRB1, HLA-DRB5, HLA-DQA1, HLA-DQB1, HLA-DOB, and TAP-2. The results suggest that genetic variations within particular MHC genes can influence immune response to common childhood vaccinations, which in turn may influence vaccine efficacy.     

Preclinical safety and immunogenicity evaluation of a nonavalent PorA native outer membrane vesicle vaccine against serogroup B meningococcal disease

Background

An improved nonavalent PorA native outer membrane vesicle vaccine was developed with intrinsic adjuvating activity due to presence of less-toxic (lpxL1) LPS. In the present study, the safety and immunogenicity of this next-generation NonaMen vaccine were evaluated following repeated vaccination in rabbits and mice.

Methods

A repeated–dose toxicology study was performed in rabbits. Immunogenicity of next-generation NonaMen was evaluated by determining the serum bactericidal antibody (SBA) titers against meningococcal serogroup B strains containing several PorA subtypes. Release of the pro-inflammatory cytokine, interleukin-6 (IL-6), by the human monocytic cell line (MM6) was measured to estimate pyrogenic activity.

Results

No toxicologically relevant findings were noted in vaccinated rabbits receiving plain next-generation NonaMen. In agreement, next-generation NonaMen induced reduced amounts of the pro-inflammatory cytokine, IL-6, released by human monocyte cell line. In both rabbits and mice, next-generation NonaMen induced high SBA titers against all tested MenB strains regardless of whether or not aluminium phosphate adjuvant is used.

Conclusions

The data suggest that next-generation NonaMen is a safe vaccine with the potential to develop a broadly protective immune response and encourage the start of the first clinical studies.     

Completion and compliance of childhood vaccinations in the United States

BackgroundThe Advisory Committee on Immunization Practices recommends routine childhood vaccination by age 2 years, yet evidence suggests that only 2% to 26% of children receive vaccine doses at age-appropriate times (compliance). The objective of this study was to estimate vaccine completion and compliance rates between birth and age 2 years using recent, nationally representative data.MethodsUsing a sample of children aged 24 to 35 months from the 2012 National Immunization Survey (NIS), the present study examined completion and compliance of recommended childhood vaccines. A state-specific examination of vaccine completion and compliance was also conducted.ResultsAn unweighted sample of 11,710 children (weighted to 4.1 million) was selected. Approximately 70% of children completed all doses of six recommended vaccines by 24 months of age. Completion rates varied by antigen, ranging from 68% completing two or three doses of rotavirus vaccine to 92% completing three doses of inactivated poliovirus vaccine. Vaccine completion rates also varied at different measurement periods, with the lowest rates observed at 18 months. Approximately 26% of children received all doses of six recommended vaccines on time. Among the 74% of children who received at least one late dose, 39% had >7 months of undervaccination. Patterns of completion and compliance also varied by geographic region.ConclusionsCompletion of individual antigens approached Healthy People 2020 targets. However, overall completion of the recommended vaccine series and compliance with the recommended vaccination dosing schedule were low, indicating few children received vaccines at age-appropriate times. Additional clinical, policy, and educational interventions are needed to increase receipt of vaccines at optimal ages.