ChrisAnna M. Mink

Comparison of acellular and whole-cell pertussis-component diphtheria-tetanus-pertussis vaccines in infants

In a multicenter, double-blind, randomized, longitudinal study, 252 children received licensed Lederle diphtheria-tetanus toxoids and pertussis vaccine adsorbed (DTP) at 2, 4, and 6 months of age, and 245 children received a DTP vaccine with the Lederle/Takeda acellular pertussis component (APDT) at the same ages. Both groups of children received APDT vaccine at 18 months of age. After each of the first three immunizations, APDT vaccine recipients had fewer local and systemic reactions than did DTP vaccinees. Reactions after the 18-month APDT vaccination were minimal in severity regardless of the vaccine previously received. Antibody responses to lymphocytosis-promoting factor and agglutinogens were more pronounced in DTP recipients; however, APDT recipients had a better serologic response to filamentous hemagglutinin, and responses to the 69K protein were equivalent. This APDT vaccine produces fewer reactions than the standard whole-cell DTP vaccine. The protective significance of the serologic responses to the APDT vaccine is unknown, but the greater response to filamentous hemagglutinin and equivalent response to the 69K protein compared with those to DTP vaccine seem promising.

Comparison of an acellular pertussis-component diphtheria-tetanus-pertussis (DTP) vaccine with a whole-cell pertussis-component DTP vaccine in 17- to 24-month-old children, with measurement of 69-kilodalton outer membrane protein antibody

Healthy 17- to 24-month-old children, previously immunized with three doses of whole-cell diphtheria-tetanus-pertussis (DTP) vaccine, were enrolled in a multi-center double-blind, randomized study comparing a DTP vaccine with an acellular pertussis-component (APDT) and a conventional whole-cell pertussis-component DTP vaccine. Thirty-eight children received APDT vaccine, and 37 children received DTP vaccine. APDT vaccine recipients had significantly less local pain and warmth than DTP vaccine recipients. Antibody responses to lymphocytosis-promoting factor were similar in the two groups. The APDT vaccine recipients had a higher IgG antibody response to filamentous hemagglutinin than the DTP vaccinees had. Equivalent agglutinin responses were seen in the two groups. The APDT vaccine recipients had a significantly better antibody re-enzyme-linked immunosorbent assay, than DTP vaccinees had 1 month and 1 year after immunization. This APDT vaccine was immunogenic and caused fewer local reactions than conventional DTP vaccine when administered as a fourth dose to 17- to 24-month-old children.

Safety and Immunogenicity of Inactivated, Vero Cell Culture-Derived Whole Virus Influenza A/H5N1 Vaccine Given Alone or with Aluminum Hydroxide Adjuvant in Healthy Adults

Dosage-sparing strategies, adjuvants and alternative substrates for vaccine production are being explored for influenza vaccine development. We assessed the safety and immunogenicity of a Vero cell culture-grown inactivated whole virus influenza A/H5N1 vaccine with or without aluminum hydroxide adjuvant [Al(OH)(3)] in healthy young adults. Vaccines were well tolerated, but injection site discomfort was more frequent in groups receiving Al(OH)(3). Dose-related increases in serum antibody levels were observed. Neutralizing antibody titers varied significantly when tested by two different laboratories. Al(OH)(3) did not enhance HAI or neutralizing antibody responses, and contributed to increased injection site pain. Because influenza antibody titers vary significantly between different laboratories, international standardization of assays is warranted.

International Bordetella pertussis assay standardization and harmonization meeting report. Centers for Disease Control and Prevention, Atlanta, Georgia, United States, 19–20 July 2007

Abstract An international meeting on Bordetella pertussis assay standardization and harmonization was held at the Centers for Disease Control and Prevention (CDC), Atlanta, GA, 19–20 July 2007. The goal of the meeting was to harmonize the immunoassays used for pertussis diagnostics and vaccine evaluation, as agreed upon by academic and government researchers, regulatory authorities, vaccine manufacturers, and the World Health Organization (WHO). The primary objectives were (1) to provide epidemiologic, laboratory, and statistical background for support of global harmonization; (2) to overview the current status of global epidemiology, pathogenesis and immunology of pertussis; (3) to develop a consensus opinion on existing gaps in understanding standardization of pertussis assays used for serodiagnosis and vaccine evaluation; and (4) to search for a multicenter process for addressing these priority gaps. Presentations and discussions by content experts addressed these objectives. A prioritized list of action items to improve standardization and harmonization of pertussis assays was identified during a group discussion at the end of the meeting. The major items included: (1) to identify a group that will organize, prepare, maintain, and distribute proficiency panels and key reagents such as reference and control sera; (2) to encourage the development and identification of one or more reference laboratories that can serve as an anchor and resource for other laboratories; (3) to define a performance-based assay method that can serve as a reference point for evaluating laboratory differences; (4) to develop guidance on quality of other reagents, e.g., pertussis toxin and other antigens, and methods to demonstrate their suitability; (5) to establish an international working group to harmonize the criteria to evaluate the results obtained on reference and proficiency panel sera; (6) to create an inventory to determine the amount of appropriate and well-characterized sera that are available globally to be used as bridging reagents for vaccine licensure; and (7) to seek specific guidance from regulatory authorities regarding the expectations and requirements for the licensure of new multicomponent pertussis vaccines.

Shift in the epidemiology of pertussis infection: an indication for pertussis vaccine boosters for adults?

Pertussis vaccination of young children has been effective in reducing the overall disease burden due to Bordetella pertussis in many countries. However, the disease has not been eliminated, although humans are the only known host of this pathogen. In fact, in some countries, the number of reported cases has increased dramatically from their nadir and epidemics routinely occur. In areas where >80% of children <2 years of age have been vaccinated, the burden of disease has shifted from elementary school-aged children (who are presumably protected by vaccination) to young infants (<6 months of age) and individuals >11 years of age. With the recent availability of acellular pertussis vaccines for older children to adults, consideration of a change in current vaccination policy is necessary in order to provide better disease control.

Effectiveness of hospital-based postpartum procedures on pertussis vaccination among postpartum women

OBJECTIVE Pertussis causes significant morbidity among adults, children, and especially infants. Since 2006, pertussis vaccination has been recommended for women after delivery. We conducted a prospective, controlled evaluation of in-hospital postpartum pertussis vaccination of birth mothers from October 2009 through July 2010 to evaluate the effectiveness of hospital-based procedures in increasing postpartum vaccination. STUDY DESIGN The intervention and comparison hospitals are private community facilities, each with 2000-6000 births/year. At the intervention hospital, physician opt-in orders for tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) before discharge were implemented in November 2009, followed by standing orders in February 2010. The comparison hospital maintained standard practice. Randomly selected hospital charts of women after delivery were reviewed for receipt of Tdap and demographic data. We evaluated postpartum Tdap vaccination rates and conducted multivariate analyses to evaluate characteristics that are associated with vaccination. We reviewed 1264 charts (658 intervention hospital; 606 comparison hospital) from women with completed deliveries. RESULTS Tdap postpartum vaccination was 0% at both hospitals at baseline. In the intervention hospital, the introduction of the opt-in order was followed by an increase in postpartum vaccination to 18%. The introduction of the standing order approach was followed by a further increase to 69% (P < .0001). No postpartum Tdap vaccinations were documented in the comparison hospital. Postpartum Tdap vaccination in the intervention hospital did not differ by demographic characteristics. CONCLUSION In-hospital ordering procedures substantially increased Tdap vaccination coverage in women after delivery. Opt-in orders increased coverage that increased substantially with standing orders.

Metabolic and Hematologic Effects and Immune Complex Formation Related to Pertussis Immunization

ABSTRACT: Selected metabolic, hematologic, and immunologic functions were evaluated in 3- to 6-mo-old Finish infants who received whole-cell pertussis-component diphtheria and tetanus toxoids and pertussis vaccine, adsorbed (DTP) vaccine, and in 4- to 6-y-old Los Angeles children who received either a licensed DTP vaccine or an acellular pertussis component DTP vaccine. One d after immunization, there was an increase in total leukocytes and neutrophils and a decrease in lymphocytes in all vaccinees. In 4- to 6-y-old children the leukocytosis and neutrophilia were greater in recipients who received the standard DTP vaccine than in vaccinees who received an acellular pertussis component DTP vaccine. In infants there was an increase in the mean plasma insulin concentration but no change in the glucose concentration 24 h after immunization; no increase in the mean plasma insulin was noted in the 4- to 6-y-old children. Three 4- to 6-y-old vaccinees had higher circulating immune complex concentrations after immunization and two of these children had high clinical reaction scores. The etiology of adverse reactions after DTP immunization is multifactorial. In contrast with findings in animals, our findings do not demonstrate a clinically significant effect due to lymphocytosis-promoting factor on glucose metabolism in vaccinated children. Neutrophilia in vaccinees is probably due to endotoxin, and some reactions may be due to circulating immune complexes.

Infections in child-care facilities and schools.

1. ChrisAnna M. Mink, MD* 2. Sylvia Yeh, MD† 1. *Clinical Professor of Pediatrics, UCLA, Los Angeles, Calif 2. †Associate Clinical Professor of Pediatrics, UCLA, Los Angeles, Calif After completing this article, readers should be able to: 1. Recognize the common infectious agents that cause outbreaks in group settings for children. 2. Describe the approaches for preventing outbreaks of infectious diseases in child care and schools. 3. Discuss tactics for managing children after exposures to specific common pediatric pathogens. In the United States in 2006, approximately 54% of the 23.7 million children younger than 5 years of age attended a child-care facility, and 55 million children attended school from kindergarten through 12th grade. (1)(2) Children cared for in child-care settings have an increased rate of infectious diseases. (3)(4) Prevention and control of infectious diseases among children in out-of-home group settings is a concern for families, staff, health-care practitioners, and the community. Several factors influence the risks for introduction and spread of infections in child-care settings. These factors include the personal hygiene and health status of the caregivers and the children (as well as their ages) and the condition of the facility (eg, environmental sanitation, space and quality, food-handling practices, policies for attendance, and ratio of children to caregivers). The characteristics of the infectious agent also are important variables that determine its potential to spread in a group setting. These factors include the organisms infectivity for the population, methods available for prevention (eg, vaccination), ability of the microbe to survive in the environment, and the mode of transmission. Modes of transmission include respiratory, fecal-oral, and contact with blood or body fluids. Other potential sources of infection are animals and fomites. ### Mechanisms for Prevention The optimal strategy for controlling infectious diseases is prevention. Standard precautions (Table 1) should be used routinely in caring for children of all ages in all group settings. (3)(4) The critical role of hand washing cannot be overemphasized. Additional measures include preventive health care for attendees …

Obstetrical Healthcare Personnel's Attitudes and Perceptions on Maternal Vaccination with Tetanus-Diphtheria-Acellular Pertussis and Influenza

Objectives. To assess perceptions of obstetrical healthcare personnel (HCP) regarding routine delivery of Tdap and influenza vaccines to pregnant and postpartum women and identify perceived barriers to vaccination. Methods. Anonymous Web-based survey of obstetricians and nurses caring for pregnant and/or postpartum women. Results. We contacted 342 HCP and received 163 (48%) completed surveys (33/142 (23%) obstetricians, 130/200 (65%) nurses). Among obstetricians, 72% and 63% thought it was “beneficial” to immunize postpartum women against influenza and pertussis, respectively. Only 8% reported vaccinating >75% of pregnant women in their care against influenza. Similarly, <1% of obstetricians reported vaccinating against pertussis. Of all HCP surveyed, 92% and 58% were familiar with ACIP recommendations for influenza and pertussis, respectively. Reported perceived barriers included patient refusal to be vaccinated, reimbursement difficulties, and discomfort in providing vaccine education. Ninety-four percent of respondents agreed that standing orders would be helpful to ensure postpartum vaccination. Conclusions. HCP were less familiar with ACIP recommendations for Tdap compared to influenza vaccines. Substantial discrepancy existed between perceived benefit of vaccination and reported immunization practices. Most identified barriers could be addressed with provider training; however, other barriers require review and changes in systematic policies related to vaccine reimbursement.