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Kathryn M Edwards

Publications and source records attributed to Kathryn M Edwards.

At least 19 recordsLinked to original sources
PubMed2026

Transcriptomic and proteomic signatures following AS03-adjuvanted Influenza A/H7N9 vaccine.

INTRODUCTION: Vaccines targeting avian influenza virus A/H7N9 are poorly immunogenic. While the immune responses can be improved with oil-in-water emulsion adjuvants such as Adjuvant System 03 (AS03), the cellular mechanisms underpinning the adjuvant effect are incompletely characterized and poorly understood. METHODS: We enrolled 30 healthy adult participants and used RNA sequencing and quantitative proteomics to characterize the response to two doses of the influenza A/H7N9 vaccine, with and without AS03, in six immune cell types. These responses were compared to those seen after administration of an unadjuvanted seasonal in uenza A/H3N2 variant vaccine to identify signatures unique to adjuvanted influenza vaccines and correlated with later antibody responses. Transcriptomic and proteomic analyses revealed that. RESULTS: AS03-adjuvanted vaccine was associated with upregulation of immune pathways in innate immune cells within 24h following vaccination for phagocytosis, antigen presentation and processing, inflammasome activation, NK-cell mediated cytotoxicity, IgA production, and interferon-response pathways. Moreover, while major histocompatibility complex (MHC I and II) upregulation was observed across multiple immune cell types, MHCII gene transcription was also increased in the neutrophil compartment, generating the hypothesis that neutrophils may play a more important role in antigen presentation than previously understood. DISCUSSION: Taken together, these data provide a more complete mechanistic understanding of oil-in-water adjuvants and their role in enhancing the immune response for pandemic influenza preparedness. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT02921997?term=NCT02921997&viewType, idientifier NCT02921997.

Adult↗
PubMed2007

Accuracy and interpretation of rapid influenza tests in children.

BACKGROUND: Influenza rapid antigen detection (rapid tests) can provide timely identification of infection and aid in clinical decision-making. Although the interpretation of test results depends on test characteristics and influenza prevalence, this information is limited in routine clinical practice. OBJECTIVE: We sought to assess the times at which rapid tests are most predictive of influenza infection. METHODS: The New Vaccine Surveillance Network enrolled children aged < 5 years who were hospitalized with respiratory symptoms or fever from October 2000 through September 2004. Nasal and throat swabs were obtained, and influenza virus was detected by culture and reverse-transcription polymerase chain reaction. Provider-ordered rapid influenza tests were compared with the criterion standard (culture and reverse-transcription polymerase chain reaction) to determine their sensitivity and specificity. The New Vaccine Surveillance Network also enrolled children in outpatient settings during the 2002-2003 and 2003-2004 influenza seasons and determined the weekly influenza prevalence among symptomatic children. Trends in weekly predictive values of the rapid tests were estimated over the influenza seasons. RESULTS: Rapid influenza tests had an overall sensitivity of 63% and specificity of 97%. In 2002-2003, the prevalence of influenza in symptomatic outpatient children peaked at 21% and stayed above 10% for approximately 4 weeks. In contrast, in 2003-2004, influenza prevalence peaked at 60% and remained above 20% for approximately 6 weeks. The positive predictive value of the rapid tests approached 80% when influenza prevalence was > or = 15% but decreased to < 70% when influenza prevalence was < 10%. CONCLUSIONS: Influenza prevalence varies between and within seasons. On the basis of our estimates, rapid tests are of limited use when prevalence is < 10%. The appropriate interpretation of rapid influenza tests requires local influenza surveillance and timely communication of this information to the practitioners.

Antigens, Viral↗
PubMed2006

Optimal bandaging of smallpox vaccination sites to decrease the potential for secondary vaccinia transmission without impairing lesion healing.

OBJECTIVE: To assess the optimal method for covering smallpox vaccination sites to prevent transmission of vaccinia. DESIGN: Randomized, nonblinded clinical trial. SETTING: Tertiary care medical center. PARTICIPANTS: Vaccinia-naive and vaccinia-experienced volunteers. INTERVENTIONS: After vaccination, study participants were randomized to receive 1 of 3 types of bandage: gauze, occlusive with gauze lining, or foam. Vaccination sites were assessed every 3 to 5 days until the lesion healed. During each visit, specimens were obtained from the vaccination site, the bandage surface before removal, and the index finger contralateral to the vaccination site and were cultured for vaccinia. Time to lesion healing was assessed. RESULTS: All 48 vaccinia-naive and 47 (87%) of 54 vaccinia-experienced participants developed a vesicle or pustule at the injection site 6-11 days after vaccination. Fourteen (14%) of 102 participants had bandage cultures positive for vaccinia. All but 1 of these vaccinia-positive cultures were of a bandage from participants randomized to the gauze bandage group, and all but 3 were of bandages from vaccinia-naive participants. No finger-specimen cultures were positive for vaccinia. One episode of neck autoinoculation occurred in a vaccinia-naive individual who had vaccinia recovered from his gauze bandage on multiple visits. The foam bandage was associated with more local adverse effects (skin irritation and induration). The time to healing did not differ among the bandage groups. CONCLUSIONS: The potential for transmission of vaccinia from a vaccination site is greater if the site is covered by gauze than if it is covered by occlusive or foam bandages. Use of an occlusive bandage with a gauze lining is the best choice for coverage of smallpox vaccination sites because of a reduced potential for vaccinia transmission and a lower reactogenicity rate. Bandage choice did not affect vaccination lesion healing.

Adult↗
PubMed2006

Cytokine expression patterns associated with systemic adverse events following smallpox immunization.

Vaccinia virus is reactogenic in a significant number of vaccinees, with the most common adverse events being fever, lymphadenopathy, and rash. Although the inoculation is given in the skin, these adverse events suggest a robust systemic inflammatory response. To elucidate the cytokine response signature of systemic adverse events, we used a protein microarray technique to precisely quantitate 108 serum cytokines and chemokines in vaccine recipients before and 1 week after primary immunization with Aventis Pasteur smallpox vaccine. We studied 74 individuals after vaccination, of whom 22 experienced a systemic adverse event and 52 did not. The soluble factors most associated with adverse events were selected on the basis of voting among a committee of machine-learning methods and statistical procedures, and the selected cytokines were used to build a final decision-tree model. On the basis of changes in protein expression, we identified 6 cytokines that accurately discriminate between individuals on the basis of adverse event status: granulocyte colony-stimulating factor, stem cell factor, monokine induced by interferon-gamma (CXCL9), intercellular adhesion molecule-1, eotaxin, and tissue inhibitor of metalloproteinases-2. This cytokine signature is characteristic of particular inflammatory response pathways and suggests that the secretion of cytokines by fibroblasts plays a central role in systemic adverse events.

Adolescent↗
PubMed2006

Cellular immune responses to diluted and undiluted aventis pasteur smallpox vaccine.

BACKGROUND: Recent primary vaccine trials of diluted Aventis Pasteur smallpox vaccine (APSV) demonstrated that immunization "take" rates, defined by the presence of a vesicle or pustule ("take") at the inoculation site 6-11 days after immunization, did not differ between the dilution groups. To our knowledge, there have been no studies that examine the cellular immune response or that distinguish CD4(+) T cell responses from CD8(+) T cell responses after primary immunization with varying dilutions of APSV. METHODS: In the present study, we examined the cellular immune response in vaccinia-naive healthy adults (n=91) receiving inoculations with an undiluted or diluted (1:5 and 1:10) suspension of the APSV, using an intracellular cytokine staining assay. RESULTS: The diluted vaccine induced vaccinia virus (VV)-specific CD4(+) and CD8(+) T cell responses 1 month after primary immunization that were comparable to those induced by undiluted vaccine. The cellular immune responses were correlated with the reactogenicity profile of subjects and did not differ between dilution groups. Furthermore, expression of the interleukin-7 receptor alpha chain, which has been proposed to distinguish antigen-specific T cells that differentiate into long-lived memory T cells, did not differ among groups, suggesting that dilution of the vaccine does not affect the quantity of VV-specific memory T cells. CONCLUSIONS: APSV is an effective smallpox vaccine inducing strong humoral and cellular immune responses after a primary immunization even at diluted doses.

CD4-Positive T-Lymphocytes↗
PubMed2006

The underrecognized burden of influenza in young children.

BACKGROUND: The disease burden of influenza infection among children is not well established. We conducted a population-based surveillance of medical visits associated with laboratory-confirmed influenza. METHODS: Eligible children were younger than five years of age, resided in three U.S. counties, and had a medical visit for an acute respiratory tract infection or fever. Nasal and throat swabs were tested for the influenza virus by viral culture and polymerase-chain-reaction assay. Epidemiologic data were collected from parental surveys and chart reviews. Children who were hospitalized were enrolled prospectively from 2000 through 2004. Population-based rates of hospitalizations associated with influenza were calculated. Children who were seen in selected pediatric clinics and emergency departments during two influenza seasons (2002-2003 and 2003-2004) were systematically enrolled. The rates of visits to clinics and emergency departments associated with influenza were estimated. RESULTS: The average annual rate of hospitalization associated with influenza was 0.9 per 1000 children. The estimated burden of outpatient visits associated with influenza was 50 clinic visits and 6 emergency department visits per 1000 children during the 2002-2003 season and 95 clinic visits and 27 emergency department visits per 1000 children during the 2003-2004 season. Few children who had laboratory-confirmed influenza were given a diagnosis of influenza by the treating physician in the inpatient (28 percent) or outpatient (17 percent) settings. CONCLUSIONS: Among young children, outpatient visits associated with influenza were 10 to 250 times as common as hospitalizations. Few influenza infections were recognized clinically.

Ambulatory Care↗
PubMed2006

Pertussis serostatus among neonates born to Hispanic women.

The reasons for the higher pertussis incidence among Hispanic infants, compared with among infants of other ethnicities, are unknown. The geometric mean concentration of pertussis toxin-specific immunoglobulin G in serum samples from 220 Hispanic neonates was 8.45 EU/mL, as determined by enzyme-linked immunosorbent assay, and it was significantly lower if mothers were adolescents (4.63 EU/mL; P < or =.001). A lack of maternal immunity is one explanation for pertussis susceptibility in very young Hispanic infants.

Adolescent↗
PubMed2006

Multicentre surveillance of the prevalence and molecular epidemiology of macrolide resistance among pharyngeal isolates of group A streptococci in the USA.

OBJECTIVES: Rates of macrolide resistance in group A streptococci (GAS) were reported to be low in the US in the 1990s. However, we documented an unexpectedly high rate of macrolide resistance among GAS in Pittsburgh, PA, in 2001 and 2002. In an effort to define the current prevalence of macrolide-resistant GAS in the US, a multicentre surveillance project was initiated. METHODS: Between October 2002 and May 2003, 50 pharyngeal GAS isolates per month were requested from each of the nine participating sites representing a wide geographical distribution. Standard susceptibility testing was performed and the macrolide resistance phenotype was assessed using double-disc diffusion testing. Monthly and annual rates of macrolide resistance were calculated for each site. An adjusted overall rate of macrolide resistance was determined to account for differences in the numbers of GAS isolates sent from each centre. RESULTS: Overall, 171 of the 2797 collected isolates of GAS (6.1%) were resistant to erythromycin. The adjusted overall resistance rate was 5.2%. Rates of macrolide resistance varied by site (range 3.0-8.7%) and also by month (<2% to >10%). The M phenotype of macrolide resistance accounted for >60% of all macrolide-resistant isolates recovered in this study. CONCLUSIONS: These data suggest an increasing prevalence and broad geographical distribution of macrolide-resistant GAS in the US, indicating the need for ongoing local and national longitudinal surveillance to define the extent of this problem.

Anti-Bacterial Agents↗
PubMed2006

Extensive swelling reaction associated with diphtheria and tetanus toxoids and acellular pertussis vaccine.

Although extensive swelling reactions in the injected limb after the administration of diphtheria-tetanus toxoid-acellular pertussis vaccine have been reported previously, to our knowledge, computerized tomography images of this entity have not been published. A 4-year-old boy with extensive swelling after vaccination with diphtheria-tetanus toxoid-acellular pertussis vaccine is presented.

Child, Preschool↗
PubMed2006

Leukopheresis therapy for severe infantile pertussis with myocardial and pulmonary failure.

OBJECTIVE: To describe an infant with severe pertussis successfully treated with leukopheresis. DESIGN: Case report. SETTING: Pediatric intensive care unit of a children's hospital. PATIENT: Five-wk-old female with pertussis complicated by cardiorespiratory failure. INTERVENTIONS: Single leukopheresis treatment. MEASUREMENTS AND MAIN RESULTS: Normalization of the white blood cell count and marked cardiorespiratory improvement after treatment; patient survived. CONCLUSION: Given the temporal association between treatment and improvement, we hypothesize that the markedly elevated white blood cell count has a major role in the cardiopulmonary compromise.

Cardiac Output, Low↗
PubMed2006

Multicenter surveillance of invasive meningococcal infections in children.

OBJECTIVES: Meningococcal disease continues to result in substantial morbidity and mortality in children, but there is limited recent surveillance information regarding serogroup distribution and outcome in children in the United States. The objective of this study was to collect demographic, clinical, laboratory, and outcome information for infants and children who had Neisseria meningitidis infections of various serogroups and were cared for in 10 pediatric hospitals. METHODS: Investigators at each of the participating hospitals identified children with meningococcal infections and collected demographic and clinical information using a standard data form. Meningococcal isolates were sent to a central laboratory for serogrouping by slide agglutination and penicillin susceptibility. RESULTS: From January 1, 2001, through March 15, 2005, 159 episodes of systemic meningococcal infections were detected. The greatest numbers of children were younger than 12 months (n = 41) or were 12 to 24 months of age (n = 22). Meningitis was the most common clinical manifestation of disease accounting for 112 (70%) cases; 43 (27%) children had bacteremia only. Children who were younger than 5 years (17 of 102) were significantly less likely to require mechanical ventilation than children who were 5 to 10 years of age (12 of 24) or children who were older than 10 years (13 of 33). Overall, 55 (44%) isolates were serogroup B, 32 (26%) were serogroup C, and 27 (22%) were serogroup Y. All but 1 isolate (intermediate) were susceptible to penicillin. The overall mortality rate was 8% (13 of 159) but was greater for children who were > or = 11 years of age (7 [21.2%] of 33) than for children who were younger than 11 years (6 [4.8%] of 126). Unilateral or bilateral hearing loss occurred in 14 (12.5%) of 112 children with meningitis. CONCLUSIONS: The morbidity and the mortality of meningococcal infections are substantial. With the recent licensure of meningococcal conjugate vaccines, our baseline trends in meningococcal disease can be compared with those seen after widespread vaccination to assess the success of routine immunization.

Adolescent↗
PubMed2006

The impact of conjugate pneumococcal vaccination on routine childhood vaccination and primary care use in 2 counties.

BACKGROUND: Pneumococcal conjugate vaccine immunization recommendations were rapidly implemented by primary care providers. Before the recommendations, concern was expressed that adding pneumococcal conjugate vaccine might result in delays in other vaccinations or preventive services. OBJECTIVES: The study objectives were to measure whether incorporation of pneumococcal conjugate vaccine by primary care providers delayed other vaccinations or added primary health care visits. DESIGN AND METHODS: In 2 counties surrounding Rochester and Nashville, we reviewed a representative sample of primary care charts for children born before and after licensure of pneumococcal conjugate vaccine. Receipt of vaccinations and health care visits were compared for the 2 age-matched cohorts. RESULTS: We reviewed 1459 records from Rochester and 1857 records from Nashville. The pre-pneumococcal conjugate vaccine and post-pneumococcal conjugate vaccine cohorts had similar demographic characteristics. The median age for receipt of any vaccination was not older for the postvaccine cohort than for the prevaccine cohort in either community. The percentage of children up-to-date for vaccinations by 18 months for postvaccine versus prevaccine cohorts was similar in Rochester (72% in each cohort) and in Nashville (58% postvaccine and 65% prevaccine). The number of well-child care visits or other health care visits during the first 18 months of life was not statistically different between the 2 cohorts. CONCLUSIONS: Implementation of pneumococcal conjugate vaccine was not associated with delays in other childhood vaccinations or more primary care visits.

Child, Preschool↗
PubMed2006

National impact of universal childhood immunization with pneumococcal conjugate vaccine on outpatient medical care visits in the United States.

BACKGROUND: Since introduction of the heptavalent pneumococcal conjugate vaccine in the United States in 2000, rates of invasive pneumococcal disease have declined. However, the national impact of heptavalent pneumococcal conjugate vaccine on pneumonia and otitis media remains unknown. OBJECTIVES: We compared national rates of outpatient visits for pneumonia and otitis media in children before and after heptavalent pneumococcal conjugate vaccine introduction. METHODS: Rates of ambulatory visits for pneumococcal and nonspecific pneumonia, otitis media, and other acute respiratory infections were compared before (1994-1999) and after (2002-2003) heptavalent pneumococcal conjugate vaccine introduction using the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. To evaluate vaccine effects while accounting for temporal variability, ratios of pneumococcal-related disease rates in children < 2 years old (vaccine target population) and in children 3 to 6 years old (not routinely vaccinated) were evaluated using a Poisson regression analysis. For children < 2 years old, the differences between observed and expected rates were the estimated vaccine effects. RESULTS: After the introduction of heptavalent pneumococcal conjugate vaccine, otitis media visit rates declined by 20% in children aged < 2 years. This decline represented 246 fewer otitis media visits per 1000 children aged < 2 years annually. There were no significant decreases in outpatient visit rates for pneumonia or other acute respiratory infections for children aged < 2 years. CONCLUSIONS: After heptavalent pneumococcal conjugate vaccine introduction, national rates of otitis media visits declined significantly in children < 2 years old. Persistence of this trend will produce a significant reduction of the otitis media burden and further enhance the cost-effectiveness of heptavalent pneumococcal conjugate vaccine.

Ambulatory Care↗
PubMed2006

Estimating influenza hospitalizations among children.

Although influenza causes more hospitalizations and deaths among American children than any other vaccine-preventable disease, deriving accurate population-based estimates of disease impact is challenging. Using 2 independent surveillance systems, we performed a capture-recapture analysis to estimate influenza-associated hospitalizations in children in Davidson County, Tennessee, during the 2003-2004 influenza season. The New Vaccine Surveillance Network (NVSN) enrolled children hospitalized with respiratory symptoms or fever and tested them for influenza. The Tennessee Emerging Infections Program (EIP) identified inpatients with positive influenza diagnostic test results through review of laboratory and infection control logs. The hospitalization rate estimated from the capture-recapture analysis in children <5 years of age was 2.4 per 1,000 (95% confidence interval 1.8-3.8). When NVSN estimates were compared with capture-recapture estimates, NVSN found 84% of community-acquired cases, EIP found 64% of cases in which an influenza rapid test was performed, and the overall sensitivity of NVSN and EIP for influenza hospitalizations was 73% and 38%, respectively.

Child, Preschool↗
PubMed2005

The role of human metapneumovirus in upper respiratory tract infections in children: a 20-year experience.

BACKGROUND: The role that human metapneumovirus (hMPV) plays in the etiology of upper respiratory tract infections (URIs) in children over a period of many years has not been evaluated previously. METHODS: By use of real-time reverse-transcriptase polymerase chain reaction, we retrospectively tested nasal wash (NW) specimens for hMPV that had been obtained from a cohort of 1532 infants and children with URIs who were prospectively followed for an average of 2.4 years during the period from 1982 to 2001. Virus genes were sequenced, and prospectively collected clinical data were analyzed. RESULTS: There were 2710 visits for URIs for which routine cultures did not reveal a viral etiology. Archival NW specimens from 2384 of these visits were available. hMPV RNA was detected in 118 (5%) of 2384 specimens. The mean age of the children with hMPV infection was 20 months, and 78% of illnesses occurred from December through May. Acute otitis media (AOM) was detected in 50% of these children. hMPV circulated each year, but the numbers of isolates detected varied by year. Reinfections with both homologous and heterologous strains occurred. Four distinct genetic lineages were present over the 20 years of surveillance, with several different lineages circulating during some seasons. CONCLUSIONS: hMPV was detected in a substantial number of children with URIs and concomitant AOM.

Child, Preschool↗