James H. Conway

Estimating the Effectiveness of Tetanus-Diphtheria-Acellular Pertussis Vaccine (Tdap) for Preventing Pertussis: Evidence of Rapidly Waning Immunity and Difference in Effectiveness by Tdap Brand

BACKGROUND We estimated the vaccine effectiveness (VE) of tetanus-diphtheria-acellular pertussis vaccine (Tdap) for preventing pertussis among adolescents during a statewide outbreak of pertussis in Wisconsin during 2012. METHODS We used the population-based Wisconsin Immunization Registry (WIR) to construct a cohort of Wisconsin residents born during 1998-2000 and collect Tdap vaccination histories. Reports of laboratory-confirmed pertussis with onset during 2012 were matched to WIR clients. Incidence rate ratios (IRRs) of pertussis and Tdap VE estimates [(1 - IRR)*100%], by year of Tdap vaccine receipt and brand (Boostrix/Adacel), were estimated using Poisson regression. RESULTS Tdap VE decreased with increasing time since receipt, with VEs of 75.3% (95% confidence interval [CI], 55.2%-86.5%) for receipt during 2012, 68.2% (95% CI, 60.9%-74.1%) for receipt during 2011, 34.5% (95% CI, 19.9%-46.4%) for receipt during 2010, and 11.9% (95% CI, -11.1% to 30.1%) for receipt during 2009/2008; point estimates were higher among Boostrix recipients than among Adacel recipients. Among Tdap recipients, increasing time since receipt was associated with increased risk, and receipt of Boostrix (vs Adacel) was associated with decreased risk of pertussis (adjusted IRR, 0.62 [95% CI, .52-.74]). CONCLUSIONS Our results demonstrate waning immunity following vaccination with either Tdap brand. Boostrix was more effective than Adacel in preventing pertussis in our cohort, but these findings may not be generalizable to adolescent cohorts that received different diphtheria-tetanus-acellular pertussis vaccines (DTaP) during childhood and should be further examined in studies that include childhood DTaP history.

The Effect of Fluoroquinolone Antibiotics on Growing Cartilage in the Lamb Model

Background: The fluoroquinolones are a relatively new class of antimicrobials with an appealing spectrum of activity. Their use in pediatric medicine is limited because of the concern over possible growth inhibition, as published reports have documented articular cartilage damage in animal models after their administration. These data, extrapolated to include the epiphyseal cartilage, suggest that these agents may reduce growth rates, but limited human data are at the least equivocal, if not strictly contradictory to such claims. Specific investigations into the effects of fluoroquinolones on epiphyseal plate cartilage and growth velocity have not been performed. Methods: Gatifloxacin and ciprofloxacin were used as representative agents of the fluoroquinolone class. Each drug was administered to experimental lambs over a 14-day interval at a dose designed to reflect those used in pediatric medicine. Recumbent versus standing intervals were used to monitor for arthropathy. Upon completion of fluoroquinolone administration, lambs underwent double fluorochrome labeling for determination of growth velocity. Gross and microscopic analysis of articular cartilage was performed to assess for pathologic changes. Age- and sex-matched lambs served as controls. Results: Neither gatifloxacin nor ciprofloxacin negatively affected growth velocity of the proximal tibial growth plate as measured by double fluorochrome labeling. In addition, no difference between experimental and control lambs in regard to recumbent versus standing intervals was noted. Examination of the articular cartilage failed to suggest chondrotoxicity. Conclusion: Fluoroquinolone antimicrobials do not affect growth velocity in the ovine model when administered along a dosing regimen that closely models that seen in pediatric medicine. Clinical Relevance: Fluoroquinolones may be acceptable for use in the pediatric population, as concerns over chondrotoxicity and growth inhibition may not be valid. These data suggest that expanded studies in lambs and other species, including humans, with differences in dosing and duration are justified to ultimately demonstrate clinical safety.

Using a Bayesian Latent Class Model to Evaluate the Utility of Investigating Persons with Negative Polymerase Chain Reaction Results for Pertussis

Pertussis remains difficult to control. Imperfect sensitivity of diagnostic tests and lack of specific guidance regarding interpretation of negative test results among patients with compatible symptoms may contribute to its spread. In this study, we examined whether additional pertussis cases could be identified if persons with negative pertussis test results were routinely investigated. We conducted interviews among 250 subjects aged ≤18 years with pertussis polymerase chain reaction (PCR) results reported from 2 reference laboratories in Wisconsin during July-September 2010 to determine whether their illnesses met the Centers for Disease Control and Preventions clinical case definition (CCD) for pertussis. PCR validity measures were calculated using the CCD as the standard for pertussis disease. Two Bayesian latent class models were used to adjust the validity measures for pertussis detectable by 1) culture alone and 2) culture and/or more sensitive measures such as serology. Among 190 PCR-negative subjects, 54 (28%) had illnesses meeting the CCD. In adjusted analyses, PCR sensitivity and the negative predictive value were 1) 94% and 99% and 2) 43% and 87% in the 2 types of models, respectively. The models suggested that public health follow-up of reported pertussis patients with PCR-negative results leads to the detection of more true pertussis cases than follow-up of PCR-positive persons alone. The results also suggest a need for a more specific pertussis CCD.

Widespread Bordetella parapertussis Infections—Wisconsin, 2011–2012: Clinical and Epidemiologic Features and Antibiotic Use for Treatment and Prevention

BACKGROUND During October 2011-December 2012, concurrent with a statewide pertussis outbreak, 443 Bordetella parapertussis infections were reported among Wisconsin residents. We examined clinical features of patients with parapertussis and the effect of antibiotic use for treatment and prevention. METHODS Patients with polymerase chain reaction results positive for B. parapertussis reported during October 2011-May 2012 were interviewed regarding presence and durations of pertussis-like symptoms and receipt of azithromycin treatment. Data regarding acute cough illnesses and receipt of azithromycin prophylaxis among parapertussis patient household members (HHMs) were also collected. Using multivariate repeated measures log-binomial regression analysis, we examined associations of treatment receipt by the HHM with the earliest illness onset and prophylaxis receipt among other HHMs with the presence of any secondary cough illnesses in the household. RESULTS Among 218 patients with parapertussis, pertussis-like symptoms were frequently reported. Illness durations were significantly shorter among patients with treatment initiated 0-6 days after cough onset, compared with nonrecipients (median durations: 10 vs 19 days, P = .002). Among 361 HHMs from 120 households, compared with nonrecipients, prompt prophylaxis of HHMs was associated with no secondary cough illnesses (relative risk: 0.16; 95% confidence interval, .04-.69). CONCLUSIONS Bordetella parapertussis infection causes pertussis-like illness that might be misclassified as pertussis if B. parapertussis testing is not performed. Prompt treatment might shorten illness duration, and prompt HHM prophylaxis might prevent secondary illnesses. Further study is needed to evaluate antibiotic effectiveness for preventing parapertussis and to determine risks and benefits of antibiotic use.

Do Maternal Knowledge and Attitudes towards Childhood Immunizations in Rural Uganda Correlate with Complete Childhood Vaccination

Improving childhood vaccination coverage and timeliness is a key health policy objective in many developing countries such as Uganda. Of the many factors known to influence uptake of childhood immunizations in under resourced settings, parents’ understanding and perception of childhood immunizations has largely been overlooked. The aims of this study were to survey mothers’ knowledge and attitudes towards childhood immunizations and then determine if these variables correlate with the timely vaccination coverage of their children. From September to December 2013, we conducted a cross-sectional survey of 1,000 parous women in rural Sheema district in southwest Uganda. The survey collected socio-demographic data and knowledge and attitudes towards childhood immunizations. For the women with at least one child between the age of one month and five years who also had a vaccination card available for the child (N = 302), the vaccination status of this child was assessed. 88% of these children received age-appropriate, on-time immunizations. 93.5% of the women were able to state that childhood immunizations protect children from diseases. The women not able to point this out were significantly more likely to have an under-vaccinated child (PR 1.354: 95% CI 1.018–1.802). When asked why vaccination rates may be low in their community, the two most common responses were “fearful of side effects” and “ignorance/disinterest/laziness” (44% each). The factors influencing caregivers’ demand for childhood immunizations vary widely between, and also within, developing countries. Research that elucidates local knowledge and attitudes, like this study, allows for decisions and policy pertaining to vaccination programs to be more effective at improving child vaccination rates.

Overcoming Challenges to Childhood Immunizations Status

Vaccines are one of the greatest public health achievements, preventing both mortality and morbidity. However, overall immunization rates are still below the 90% target for Healthy People 2020. There remain significant disparities in immunization rates between children of different racial/ethnic groups, as well as among economically disadvantaged populations. There are systemic issues and challenges in providing access to immunization opportunities. In addition, vaccine hesitancy contributes to underimmunization. Multiple strategies are needed to improve immunization rates, including improving access to vaccines and minimizing financial barriers to families. Vaccine status should be assessed and vaccines given at all possible opportunities.

Addressing vaccine hesitancy in the pharmacy.

Mary S. Hayney, PharmD,MPH, BCPS, Professor of Pharmacy, School of Pharmacy, University of Wisconsin, Madison (mary. hayney@wisc.edu) and John D. Grabenstein, PhD, Executive Director, Global Health & Medical Affairs, Merck Vaccines (john_grabenstein@merck.com). The reluctance of some to be vaccinated, termed “vaccine hesitancy,” has contributed to decreasing immunization coverage in some communities and has likely contributed to outbreaks of vaccine-preventable diseases. According to the Centers for Disease Control and Prevention (CDC), measles outbreaks in 2015 were related to 68 unvaccinated US residents, where 29 of them stated religious or philosophic reasons for not being vaccinated.1 Immunization rates for the routinely recommended influenza and pneumococcal vaccines fall far below their Healthy People 2020 goals of 70% and 60% coverage, respectively. Influenza coverage for the 2014e2015 season was reported to be 47%2,3 and pneumococcal coverage in high-risk populations aged 19 to 64 years for 2013 was only 21%.4 Vaccine hesitancy is a continuum of behavior, with most falling somewhere between acceptance of all and refusal of all vaccines available.5 To address vaccine hesitancy, pharmacists should be able to understand and recognize it. The World Health Organization (WHO) provides the following definition6: “Vaccine hesitancy refers to delay in acceptance or refusal of vaccines despite availability of vaccination services. Vaccine hesitancy is complex and context specific, varying across time, place, and vaccines. It includes factors such as complacency, convenience, and confidence.” Pharmacists play an important role not only in delivery of vaccines, but advocacy as well. This article provides valuable information for pharmacists and pharmacies to reference when confronting vaccine hesitancy. The Strategic Advisory Group of Experts (SAGE) on Vaccine Hesitancy, established to serve as an advisory group to WHO, created a matrix model to help

Update in Pediatric Musculoskeletal Infections: When It Is, When It Isn't, and What to Do.

Musculoskeletal infections, including osteomyelitis, septic arthritis, and pyomyositis, are a substantial cause of morbidity in children and adolescents. The increased virulence of infectious agents and the increased prevalence of antimicrobial-resistant pathogens, particularly methicillin-resistant Staphylococcus aureus, have resulted in a more complicated clinical course for diagnosis and management, which is evidenced by an increased length of hospital stays, incidence of complications, and number of surgical interventions. Musculoskeletal infections are a challenge for surgeons because they vary substantially in their presentation and in their required treatment, which is based on the causative organism, the location of the infection, and the age of the patient. The necessity for a prompt diagnosis is complicated by several diseases that may mimic musculoskeletal infection, including transient synovitis, autoimmune arthritis, and tumors. Recent innovations in diagnosis and management have provided surgeons with new options to differentiate musculoskeletal infections from these rapidly evolving disease pathologies. As diagnostic and treatment modalities improve, collaboration among surgeons from multiple disciplines is required to develop evidence-based clinical practice guidelines that minimize the effect of musculoskeletal infection and optimize clinical outcomes for patients.

Zika: information in the nick of time

The association of Zika virus with microcephaly and other neurologic issues has led to widespread concern throughout the world. These concerns have led local and national government health agencies to take a variety of measures to inform the public, and to prevent the spread of the virus. In Florida, for example, there was widespread spraying in a Miami neighborhood where 16 cases of autochthonous transmission had been found, and an urgent travel alert issued quickly [1]. Newspapers rapidly began urging people, especially pregnant women, to take specific precautions. They offered suggestions that included chemical clothing treatment, wearing long sleeves and pants, and even staying indoors as much as possible [2]. In February 2016, CBS reported that mosquito repellent sales in the United States had already increased by 11.9% from 2015 [3].

Thimerosal and Other Vaccine Additives

While vaccines would ideally only need to contain the antigens necessary to induce immunity, the reality of vaccine production requires the addition of other materials, sometimes called “excipients.” These excipients include a wide array of additives, usually in minute concentrations. Preservatives and other related substances are required to maintain vaccine stability and potency. Adjuvants may be necessary to induce adequate protective immunity. In addition, there are other materials sometimes introduced into the final products either as a result of the manufacturing process or packaging. The excipient materials found in vaccines have been a significant source of misunderstanding, and misinformation. Much of the controversy related to vaccine safety is a result of spurious associations between these vaccine additives and exaggerations of real, or perceived, side effects from immunization. While a few of these chemicals can be toxic in large quantities, most are only present in trace amounts in most vaccines. This chapter reviews some of the more common or controversial vaccine excipients, and related information regarding safety concerns.