Michael R. Nelson

Half- vs Full-Dose Trivalent Inactivated Influenza Vaccine (2004-2005) Age, Dose, and Sex Effects on Immune Responses

BACKGROUND Optimal public health strategies for managing influenza vaccine shortages are not yet defined. Our objective was to determine the effects of age, sex, and dose on the immunogenicity of intramuscular trivalent inactivated vaccine (TIV). METHODS Healthy adults aged 18 to 64 years, stratified by age (18-49 and 50-64 years) and sex, were randomized to receive full- or half-dose TIV. Hemagglutination inhibition titers against vaccine antigens were measured before and 21 days after immunization. A primary outcome of noninferiority was defined as a difference of less than 20% in the upper 95% confidence interval (CI) of the proportion of subjects with strain-specific hemagglutination inhibition antibody titers of 1:40 or higher after vaccination. Secondary outcomes included geometric mean titers, after vaccination side effects, and occurrences of influenza-like illnesses. RESULTS Among previously immunized subjects (N = 1114) receiving half- vs full-dose TIV (age, 18-49 years, n = 284 [half] and n = 274 [full]; and age 50-64 years, n = 276 [half] and n = 280 [full]), CIs for proportions of subjects with hemagglutination inhibition antibody titers of 1:40 or higher excluded substantial reduction for all antigens in the 18- to 49-year age group and for B/Shanghai/361/2002 (B) and A/Fujian/411/2002 (A/H3N2) in the 50- to 64-year age group. Geometric mean titer in the female 18- to 49-year age group exceeded male responses for all strains: responses to half-dose TIV that were comparable with male full-dose responses for A/New Caledonia/20/99 (A/H1N1) antigen, 25.4 (95% CI, 20.9-30.9) vs 25.6 (95% CI, 21.3-30.9); A/H3N2 antigen, 60.8 (95% CI, 50.8-72.7) vs 44.1 (95% CI, 37.6-51.8); and B antigen, 64.4 (95% CI, 53.9-76.9) vs 60.7 (95% CI, 51.4-71.7) (findings were similar for the 50- to 64-year age group). Some injection site and systemic reactions (myalgias and/or arthralgias [P < .05], headache [P < .001], and impact of fatigue [P < .05]) were significantly lower in men. The relative risk of medical visits and hospitalizations for influenza-like illnesses were similar in the half- and full-dose groups regardless of age. CONCLUSIONS Antibody responses to intramuscular half-dose TIV in healthy, previously immunized adults were not substantially inferior to the full-dose vaccine, particularly for ages 18 to 49 years. Significantly higher geometric mean titer responses in women were identified for all ages, regardless of dose or influenza strain. Half-dose vaccination may be an effective strategy for healthy adults younger than 50 years in the setting of an influenza vaccine shortage.

Allergen immunotherapy practice in the United States: guidelines, measures, and outcomes.

To discuss recent issues pertinent to allergen immunotherapy practice in the United States. Allergen extract preparation guidelines, updated allergen immunotherapy practice parameter (AIPP) guidelines, and evolving trends in how immunotherapy outcomes will be measured and assessed. Allergen extract preparation guidelines have been established by 2 entities: the US Pharmacopeia and an American Academy of Allergy, Asthma, and Immunology/American College of Allergy, Asthma, and Immunology/Joint Council of Allergy, Asthma, and Immunology Joint Task Force. Minor differences exist between these guidelines, but both focus on aseptic techniques and require that compounding personnel pass a written examination and annual media fill test. The AIPP third update provides new dosing recommendations for Bermuda grass, imported fire ant, and nonstandardized extracts distinguishing between pollen (0.5 mL of a 1:100 or 1:200 vol/vol) and mold/fungi or cockroach (highest tolerated dose) extracts. Because of limited and sometimes conflicting data on high and low proteolytic-containing extract compatibility, the AIPP continues to recommend against mixing these together. Although the AIPP does not specifically recommend a specific diluent, recent evidence suggests normal saline may not be as effective a stabilizer for extract dilutions as glycerin or human serum albumin. Currently, immunotherapy efficacy is determined with subjective assessments that rely on patient reporting, but this may change as health care reform evolves. It will likely become more important for US allergy/immunology practices to demonstrate immunotherapy comparative-effectiveness and report quality measures. Recent comparative-effectiveness studies have demonstrated the cost-effectiveness of immunotherapy compared with symptomatic drug treatment.

Managing rhinitis : Strategies for improved patient outcomes

Allergic rhinitis affects more than 40 million Americans, with estimated costs reaching

Protective Antigen-Specific Memory B Cells Persist Years after Anthrax Vaccination and Correlate with Humoral Immunity

5.3 billion annually. The global impact includes negative effects on quality of life (QOL), sleep, diminished work productivity, and exacerbation of comorbid conditions. An accurate diagnosis of allergic or nonallergic rhinitis is needed before selecting optimal treatment, which can include antihistamines, decongestants, intranasal corticosteroids, immunotherapy, and anticholinergics. It is also important to understand that pharmacologic properties of these different interventions may affect patient satisfaction, compliance, and overall clinical response. This article reviews currently available therapies for allergic rhinitis with a focus on improving patient outcomes.

Hymenoptera of Afghanistan and the central command area of operations: assessing the threat to deployed U.S. service members with insect venom hypersensitivity.

Anthrax Vaccine Adsorbed (AVA) generates short-lived protective antigen (PA) specific IgG that correlates with in vitro toxin neutralization and protection from Bacillus anthracis challenge. Animal studies suggest that when PA-specific IgG has waned, survival after spore challenge correlates with an activation of PA-specific memory B cells. Here, we characterize the quantity and the longevity of AVA-induced memory B cell responses in humans. Peripheral blood mononuclear cells (PBMCs) from individuals vaccinated ≥3 times with AVA (n = 50) were collected early (3–6 months, n = 27) or late after their last vaccination (2–5 years, n = 23), pan-stimulated, and assayed by ELISPOT for total and PA-specific memory B cells differentiated into antibody secreting cells (ASCs). PA-specific ASC percentages ranged from 0.02% to 6.25% (median: 1.57%) and did not differ between early and late post-vaccination individuals. PA-specific ASC percentages correlated with plasma PA-specific IgG (r = 0.42, p = 0.03) and toxin neutralization (r = 0.52, p = 0.003) early post vaccination. PA-specific ASC percentages correlated with supernatant anti-PA both early (r = 0.60, p = 0.001) and late post vaccination (r = 0.71, p < 0.0001). These data suggest PA-specific memory B cell responses are long-lived and can be estimated after recent vaccination by the magnitude and neutralization capacity of the humoral response.

Anaphylaxis Complicating Routine Childhood Immunization: Hemophilus Influenza b Conjugated Vaccine

Insect venom hypersensitivity can pose a threat to personnel deployed to a combat zone but the exposure risk in Afghanistan is currently unknown. This study was designed to assess the threat of Hymenoptera stings and associated allergic reactions in Afghanistan. Hymenoptera species were collected during a deployment to southern Afghanistan from June 2010 through January 2011. The literature was also reviewed to determine species of medically important Hymenoptera recorded in the region. The U.S. Army theater electronic medical data system was mined for ICD-9 codes associated with insect stings to determine the number of theater medical clinic encounters addressing insect sting reactions. Three species of flying hymenoptera were commonly encountered during the study period: Vespa orientalis L., Polistes wattii Cameron, and Vespula germanica (F.). A literature review also confirms the presence of honeybees (Apidae), numerous velvet ant (Mutillidae) species, and various ant (Formicidae) species all capable of stinging. No evidence was identified to suggest that fire ants (Solenopsis ssp.) are a threat in the region. Based on electronic medical records from the U.S. Central Command area of operations over a 2-year period, roughly 1 in 500 clinic visits involved a patient with a diagnosis of insect bite or sting. Cross-reactive members of all five flying Hymenoptera species commonly assessed for in Hymenoptera allergy evaluations are present in Afghanistan. The review of in-theater medical records confirms that insect stings pose an environmental threat to deployed service members.

Four-Year Experience with Serious Adverse Reactions to Intravenous γ-Globulin at a Tertiary Medical Center

Increasing numbers of vaccines are being introduced into the infant and childhood immunization schedules. Immediate hypersensitivity reactions to include anaphylaxis can occur during the immunization visit. Determining the cause of a vaccine-associated immediate hypersensitivity reaction may require multiple specific skin test and challenge procedures. We report the case of a 4-month-old Caucasian male who developed an urticarial rash within 10 minutes of receiving his 4-month immunizations, diphtheria-tetanus-acellular pertussis (DTaP), inactivated polio (IPV), and the diphtheria mutant protein (CRM197) conjugated Hemophilus influenzae type b (HbOC). The child was referred for an allergy-immunology consultation in order to determine the cause of the reaction and a future vaccine management strategy. Negative prick skin tests were obtained with full-strength vaccine and subsequent dose challenges with DTaP and IPV vaccines were tolerated without reaction. Prick skin testing with full-strength HbOC was neg...

Unique Inflammatory Mediators and Specific IgE Levels Distinguish Local from Systemic Reactions after Anthrax Vaccine Adsorbed Vaccination

Reports of the true incidence of adverse reactions to intravenous γ-globulin (IVIG) therapy are limited by the lack of studies documenting reactions in a large number of patients. The objective was to describe the frequency of serious side effects to intravenous immune globulin therapy at a major tertiary medical center between 1991 and 1995. A central pharmacy registry of a tertiary medical center was searched for all patients and doses of intravenous immune globulin therapy given in both the inpatient and outpatient setting. Records of patients were reviewed for specific details regarding an adverse reaction. Acute renal failure occurred in 2 of 194 (1%) patients and aseptic meningitis occurred in 4 of 194 (2%) patients. Renal failure occurred in 2 of 1637 (0.1%) of infusions and aseptic meningitis occurred in 5 of 1637 (0.3%) of infusions. Both cases of renal failure were adults receiving high doses (2 g/kg) of IVIG. Of the 4 patients who developed aseptic meningitis, 3 were adults and 1 was a child. A...

INCIDENCE OF MYOCARDITIS/PERICARDITIS FOLLOWING SMALLPOX VERSUS INFLUENZA VACCINATION

ABSTRACT Although the U.S. National Academy of Sciences concluded that anthrax vaccine adsorbed (AVA) has an adverse event (AE) profile similar to those of other adult vaccines, 30 to 70% of queried AVA vaccinees report AEs. AEs appear to be correlated with certain demographic factors, but the underlying immunologic pathways are poorly understood. We evaluated a cohort of 2,421 AVA vaccinees and found 153 (6.3%) reported an AE. Females were more likely to experience AEs (odds ratio [OR] = 6.0 [95% confidence interval {CI} = 4.2 to 8.7]; P < 0.0001). Individuals 18 to 29 years of age were less likely to report an AE than individuals aged 30 years or older (OR = 0.31 [95% CI = 0.22 to 0.43]; P < 0.0001). No significant effects were observed for African, European, Hispanic, American Indian, or Asian ancestry after correcting for age and sex. Additionally, 103 AEs were large local reactions (LLRs), whereas 53 AEs were systemic reactions (SRs). In a subset of our cohort vaccinated 2 to 12 months prior to plasma sample collection (n = 75), individuals with LLRs (n = 33) had higher protective-antigen (PA)-specific IgE levels than matched, unaffected vaccinated individuals (n = 50; P < 0.01). Anti-PA IgE was not associated with total plasma IgE, hepatitis B-specific IgE, or anti-PA IgG in individuals who reported an AE or in matched, unaffected AVA-vaccinated individuals. IP-10 was also elevated in sera of individuals who developed LLRs (P < 0.05). Individuals reporting SRs had higher levels of systemic inflammation as measured from C-reactive protein (P < 0.01). Thus, LLRs and SRs are mediated by distinct pathways. LLRs are associated with a vaccine-specific IgE response and IP-10, whereas SRs demonstrate increased systemic inflammation without a skewed cytokine profile.

Aseptic Meningitis Due to Intravenous Immunoglobulin Therapy That Resolved with Subcutaneous Administration

Over 2 million U.S. servicemembers have received smallpox vaccination (SPX) since December 2002. There is limited data on the incidence of clinical myocarditis/pericarditis (MP) following SPX and potential subclinical myocarditis has not been well defined. To determine the incidence of clinical and