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Biomedical subjects

Kathryn M Edwards

Publications and source records attributed to Kathryn M Edwards.

At least 55 records · Page 3Linked to original sources
PubMed2004

Adverse events after smallpox immunizations are associated with alterations in systemic cytokine levels.

The immunization of healthy adults with vaccinia virus (VV) induces a protective response against smallpox in most individuals but is also reactogenic in a significant number of vaccinees. The immunological mechanisms underlying the protective response or adverse events in humans are not well defined. Although cytokines contribute to antiviral immunity and, in some cases, cause systemic adverse effects, their role in the human response to VV is unknown. We investigated the effect of smallpox immunization on systemic cytokine concentrations in a cohort of VV-naive individuals. We found that smallpox immunization induces an interferon (IFN)- gamma -dominant response in the systemic compartment 1 week after immunization, with concentrations returning to baseline during convalescence. The level of IFN- gamma induced was not affected by the dilution of vaccine used. We also found that particular adverse events correlated with systemic cytokine patterns, which suggests a role for these molecules in the pathogenesis of adverse events.

Adolescent↗
PubMed2004

Evaluation of anatomic changes in young children with natural rotavirus infection: is intussusception biologically plausible?

BACKGROUND: Several studies have shown an association between vaccination with the rotavirus vaccine and the development of intussusception. We evaluated the plausibility of a causal association between natural rotavirus infection and intussusception. METHODS: We performed ultrasound measurements, in infants with confirmed rotavirus infection and in healthy control subjects, of the ileum wall thickness and mesenteric lymph nodes, at enrollment and 1 month later. RESULTS: Thirteen pairs of patients with rotavirus infection and control subjects were enrolled. The mean distal ileum wall thickness at the first examination was 3.0 mm in patients with rotavirus infection and 2.0 mm in control subjects (P = .037). The maximum lymph node size in patients with rotavirus infection was 11.6 mm at the first examination and 7.4 mm at the second examination (P = .017). Nodal aggregates and free fluid were also observed more commonly among patients with rotavirus infection (54% vs. 9%; P = .033 for both). CONCLUSION: Rotavirus infection was associated with increased distal ileum wall thickness and lymphadenopathy during the illness period. These changes suggest a plausible mechanism by which rotavirus infection could cause intussusception.

Case-Control Studies↗
PubMed2004

Superiority of reverse-transcription polymerase chain reaction to conventional viral culture in the diagnosis of acute respiratory tract infections in children.

We compared the rates of detection of respiratory viruses by reverse-transcription polymerase chain reaction (RT-PCR) and by conventional viral culture in 668 combined nasal and throat samples from a prospective, multicenter, population-based study of acute respiratory tract infections among hospitalized children aged <5 years. RT-PCR increased the yield of viral identification by 2-fold, compared with that of culture alone. The increased sensitivity of viral detection by RT-PCR will yield better estimates of the population burden of viral respiratory infections.

Acute Disease↗
PubMed2004

Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children.

BACKGROUND: We sought to determine the role of human metapneumovirus in lower respiratory tract illness in previously healthy infants and children. METHODS: We tested nasal-wash specimens, obtained over a 25-year period from otherwise healthy children presenting with acute respiratory tract illness, for human metapneumovirus. RESULTS: A viral cause other than human metapneumovirus was determined for 279 of 687 visits for acute lower respiratory tract illness (41 percent) by 463 children in a population of 2009 infants and children prospectively seen from 1976 to 2001. There were 408 visits for lower respiratory tract illness by 321 children for which no cause was identified. Of these 321 children, specimens from 248 were available. Forty-nine of these 248 specimens (20 percent) contained human metapneumovirus RNA or viable virus. Thus, 20 percent of all previously virus-negative lower respiratory tract illnesses were attributable to human metapneumovirus, which means that 12 percent of all lower respiratory tract illnesses in this cohort were most likely due to this virus. The mean age of human metapneumovirus-infected children was 11.6 months, the male:female ratio was 1.8:1, 78 percent of illnesses occurred between December and April, and the hospitalization rate was 2 percent. The virus was associated with bronchiolitis in 59 percent of cases, pneumonia in 8 percent, croup in 18 percent, and an exacerbation of asthma in 14 percent. We also detected human metapneumovirus in 15 percent of samples from 261 patients with upper respiratory tract infection but in only 1 of 86 samples from asymptomatic children. CONCLUSIONS: Human metapneumovirus infection is a leading cause of respiratory tract infection in the first years of life, with a spectrum of disease similar to that of respiratory syncytial virus.

Adolescent↗
PubMed2004

Risk of vaccinia transfer to the hands of vaccinated persons after smallpox immunization.

Transmission of vaccinia virus after smallpox vaccination is a concern. We conducted a prospective examination of the protection afforded by vaccination-site bandages in recently vaccinated individuals. After smallpox vaccination, inoculation sites were covered with 2 occlusive dressings. Site assessment and bandage changes occurred every 3-5 days until the site was healed. At each visit, specimens from the vaccination site, outer dressing surface, and contralateral hand were obtained for vaccinia culture. For 148 vaccinated subjects, vaccinia was detected from vaccination lesions of every subject on several occasions. Only 6 (0.65%) of 918 dressing (95% CI, 0.24%-1.4%) and 2 (0.22%) of 926 hand (95% CI, 0.03%-0.78%) specimens tested positive for vaccinia. The mean number of bandage changes was 9.6 (95% CI, 9.17-10.0). Vaccinia autoinoculation did not occur. The rate of vaccinia recovery outside occlusive bandages covering smallpox vaccination sites was remarkably low, suggesting excellent protection against inadvertent transmission.

Adult↗
PubMed2004

Immune responses to influenza immunization in children receiving maintenance chemotherapy for acute lymphoblastic leukemia.

PURPOSE: To compare the immune responses to influenza vaccine in children with acute lymphoblastic leukemia (ALL) receiving maintenance chemotherapy with those in healthy children. METHODS: Hemagglutinin-inhibition (HAI) antibody titers were determined before and after influenza vaccination in children with ALL and healthy controls. Immune responses were measured as geometric mean titers (GMT) and 4-fold rises in HAI titers. RESULTS: Although post-immunization GMT were lower in children with ALL compared to healthy children for the H1N1 antigen (P<0.001), the H3N2 antigen (P=0.03), and for the influenza B antigen (P=0.003), at least 60% of children with ALL had at least a 4-fold rise in HAI titers to each of the influenza antigens. CONCLUSIONS: While the GMT after trivalent influenza immunization in children with ALL were significantly lower than those seen in healthy children, the majority of children with ALL had 4-fold rises in HAI titers. Children receiving maintenance chemotherapy for ALL should receive yearly influenza vaccine.

Antibodies, Viral↗
PubMed2004

Differences in antibiotic prescribing patterns for children younger than five years in the three major outpatient settings.

OBJECTIVES: To perform a comprehensive analysis of the use of antibiotics in three major sites for outpatient care: private office-based clinics, emergency departments (ED), and hospital-based clinics. STUDY DESIGN: Data from the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) were used to determine visit rates and antibiotic prescribing patterns for the three major outpatient care settings from 1994 to 2000 for children <5 years of age. RESULTS: Antibiotic prescription rates declined from 1405 to 1088 per 1000 children over the study years (P=.032) [correction]. Significant declines in antibiotic prescriptions were noted in both the office-based setting and ED: 1119 to 841 (P=.049) in the office-based setting and 237 to 198 antibiotic prescriptions per 1000 children in the ED (P=.003) [correction]. Sites of care differed markedly with white children receiving 82.5%, 14.3%, and 3.2% of antibiotics in the office-based settings, ED, and hospital-based clinics, respectively, compared with 60%, 31%, and 9% for black children (P<.001). However, total visits, visits resulting in a diagnosis of otitis media, and antibiotic prescribing rates were similar for white and black children during the latter study years. CONCLUSIONS: There has been a decline in antibiotic prescribing in children <5 years of age, which was most notable in office-based and emergency department settings.

Ambulatory Care Facilities↗
PubMed2004

Elimination of racial differences in invasive pneumococcal disease in young children after introduction of the conjugate pneumococcal vaccine.

BACKGROUND: Racial differences in the epidemiology of invasive pneumococcal disease (IPD) have been widely recognized, but the impact of conjugate pneumococcal vaccine (PCV) introduction in 2000 on these differences has not been extensively studied. METHODS: IPD episodes in 5 Tennessee counties from January 1995 through December 2002 were collected prospectively using the Centers for Disease Control and Prevention's Active Bacterial Core Surveillance system (ABCs). Trained nurses collected clinical data, and antibiotic susceptibility testing was performed on available isolates. RESULTS: Before vaccine licensure, IPD rates were highest in children younger than 2 years and in blacks. The disparity in IPD rates between blacks and whites younger than 2 years of age substantially diminished after PCV introduction. In 1999, the IPD rate in black children younger than 2 years was 340.2 per 100,000, representing 176.5 more events per 100,000 than in white children (P < 0.001). In 2002, this rate had decreased 83% to 57.4 per 100,000, similar to the rate in white children (39.6 per 100,000; P = 0.31). Before vaccine licensure, a higher percentage of isolates from whites were antibiotic-nonsusceptible. In 2002, the proportion of antibiotic-nonsusceptible pneumococcal isolates was similar in whites and blacks of all ages for the first time during the study period (P > 0.05 for separate comparisons of penicillin, cephalosporin and erythromycin nonsusceptibility). These changes occurred despite a lower PCV vaccination coverage in Tennessee in blacks than in whites (31.2% versus 47.6%). CONCLUSIONS: With conjugate pneumococcal vaccine introduction in Tennessee, racial differences in the incidence rates of IPD have largely been eliminated, particularly in young children.

Adolescent↗
PubMed2004

Establishment of diagnostic cutoff points for levels of serum antibodies to pertussis toxin, filamentous hemagglutinin, and fimbriae in adolescents and adults in the United States.

Numerous reports have documented that serologic methods are much more sensitive than culture for the diagnosis of pertussis in adolescents and adults. However, a standardized serologic test for pertussis is not routinely available to most clinicians, and the serologic test levels or cutoff points correlated with diseases have not been determined. The goal of the present study was to examine the distribution of immunoglobulin G (IgG) levels against three Bordetella pertussis antigens (pertussis toxin [PT], filamentous hemagglutinin [FHA], and fimbria types 2 and 3 [FIM]) and to determine population-based antibody levels for the purpose of establishing such diagnostic cutoff points. Enzyme-linked immunosorbent assays (ELISAs) were performed with sera from >6,000 U.S. residents aged 6 to 49 years who participated in the Third National Health and Nutrition Examination Survey. Mixture models were developed to identify hypothesized exposure groups and establish diagnostic cutoffs. Quantifiable (>20 ELISA units/ml [EU]) anti-FHA and anti-FIM IgG antibodies were common (65 and 62% of individuals, respectively), but quantifiable anti-PT IgG antibodies were less frequent (16%). Given the distributions of antibody levels, an anti-PT IgG level of > or =94 EU was proposed as the diagnostic cutoff point. Application of this cutoff point to culture-confirmed illness in a prior study investigating cough illness yielded a high diagnostic sensitivity (80%) and specificity (93%). A standardized ELISA for anti-PT IgG with a single serum sample appears to be useful for the identification of recent B. pertussis infection in adolescents and adults with cough illness. The PT cutoff point will be further evaluated in prospective studies of confirmed B. pertussis infection.

Adolescent↗
PubMed2004

Surveillance of childhood influenza virus infection: what is the best diagnostic method to use for archival samples?

Despite the clinical importance of influenza virus in pediatric respiratory infections, the optimal set of diagnostic tests to use when conducting studies using archival samples is not clear. In this study, we compared diagnostic tests for influenza virus in 75 children younger than 5 years of age who presented with symptomatic respiratory infection during one of four influenza seasons, had negative viral cultures for other respiratory pathogens, and had both an archival nasal aspirate obtained at the time of illness and serology spanning that influenza season. For all eligible children, we compared the results of viral culture performed at the time of collection with serology and PCR of archival nasal aspirates. Using real-time viral culture as the "gold standard," the test characteristics of PCR of archival nasal aspirates (sensitivity, 82%; specificity, 100%) and serology (sensitivity, 82%; specificity, 87%) were similar. The relatively low sensitivity of PCR of archival nasal samples in this study compared to that of PCR of fresh samples in a previous study suggests that RNA degradation occurred despite storage of the specimens at -70 degrees C. RNA degradation would also explain why only 11 (52%) of 21 archival nasal samples that had positive influenza virus cultures at the time of collection had positive repeat cultures in the summer of 2000. Thus, in archival specimens stored at -70 degrees C, PCR was more sensitive than viral culture. However, testing of fresh specimens had the highest yield in this study. Studies of optimal methods for specimen storage are needed.

Child, Preschool↗
PubMed2004

Population-based surveillance for hospitalizations associated with respiratory syncytial virus, influenza virus, and parainfluenza viruses among young children.

OBJECTIVE: Respiratory syncytial virus (RSV), influenza virus, and parainfluenza viruses (PIV) cause significant morbidity in young children. Although only influenza virus infection and illness is currently vaccine-preventable, vaccines are under development for RSV and PIV. We established a prospective, active population-based surveillance network to provide precise estimates of hospitalization rates for viral acute respiratory illness (ARI) in young children and to measure the potential impact of enhanced vaccine usage on these rates. METHODS: Prospective, active population-based surveillance was conducted in young children who were hospitalized for ARI from October 1, 2000, to September 30, 2001, in Monroe County, New York (Rochester area) and Davidson County, Tennessee (Nashville area). Eligible children younger than 5 years were those who resided in surveillance counties and were hospitalized for febrile or acute respiratory illness. Viral culture and polymerase chain reaction identified viruses from nasal and throat samples obtained from all surveillance children. We measured population-based rates of hospitalization for RSV, influenza virus, and PIV as well as demographic, clinical, and risk factor assessment for each virus. RESULTS: Of 812 eligible hospital admissions, 592 (73%) children were enrolled. Of the enrolled children, RSV was identified in 20%, influenza in 3%, PIV in 7%, other respiratory viruses in 36%, and no detectable virus in 39%. Population-based rates of ARI hospitalizations in children younger than 5 years were 18 per 1000. Virus-positive hospitalization rates per 1000 children were 3.5 for RSV, 1.2 for PIV, and 0.6 for influenza virus. Younger age (particularly <1 year), black and Hispanic race/ethnicity, male gender, and presence of chronic underlying illness were associated with higher hospitalization rates. CONCLUSIONS: This study confirms that children younger than 5 years and particularly children younger than 1 year have a high burden of hospitalization from RSV, influenza, and PIV. The enhanced use of influenza vaccine and the development of RSV and PIV vaccines have the potential to reduce markedly the pediatric morbidity from ARIs.

Age Distribution↗
PubMed2004

Population-based impact of pneumococcal conjugate vaccine in young children.

OBJECTIVE: To determine the population impact of pneumococcal conjugate vaccine (PCV) on pneumococcal-related diseases, including pneumonia and otitis media. METHODS: Using administrative data from Tennessee Medicaid and 3 commercial insurance plans in upstate New York, we measured annual rates of medical visits for pneumococcal-related diseases (pneumococcal and nonspecific pneumonia and invasive disease; otitis media) and pneumococcal-unrelated diseases (other acute respiratory illnesses). Disease rates before (1995-2000 in Tennessee; 1998-2000 in New York) and after (2000-2002) PCV licensure were calculated for children aged <2 years (eligible for PCV) and those 3 to 5 years (not routinely given PCV). Because annual variations should affect both age groups similarly and vaccine-related outcomes should preferentially decline in younger children, ratios (<2:3-5 years) of disease rates before and after PCV licensure were compared. Expected disease rates were calculated for children aged <2 years in each postvaccine year. The difference between observed and expected disease rates was the estimated vaccine effect. RESULTS: In 2001-2002, there were 67 380 and 9485 child-years of observation for Tennessee and New York children aged <2 years, respectively. We observed fewer visits for pneumonia and invasive disease per 1000 children than expected in both regions: 20 fewer emergency department or outpatient visits in Tennessee and 33 fewer outpatient visits in New York. Otitis media visits declined by 118 and 430 per 1000 children in Tennessee and New York, respectively. CONCLUSIONS: Adding PCV to the childhood immunization schedule was associated with a 10-fold greater reduction in pneumonia and a 100-fold greater reduction in otitis media than the previously reported reduction in culture-confirmed invasive pneumococcal diseases of 1.3 episodes per 1000 children aged <2 years. Although additional studies are needed to confirm the impact of routine immunization with PCV on pneumococcal-related disease, these results suggest that its impact is substantially greater than the effects on invasive disease alone.

Child, Preschool↗
PubMed2003

Pertussis: an important target for maternal immunization.

Cord blood antipertussis IgG concentrations were measured in infants and were found to be nearly equal to maternal levels. By 4 months of age most infants had no measurable antibody to pertussis toxin (PT) or filamentous hemagglutinin. Higher concentrations of maternally derived antibody to PT were associated with a weaker pertussis toxin antibody response to whole cell pertussis vaccine, but not to a cellular vaccine. These studies suggest that maternal immunization would provide early protection of the newborn to allow time for the primary immunization schedule at 2, 4, and 6 months of age to induce more durable protection.

Adult↗
PubMed2003

Focal and generalized folliculitis following smallpox vaccination among vaccinia-naive recipients.

CONTEXT: With the reintroduction of smallpox vaccination, detailed contemporary descriptions of adverse reactions to the vaccine are needed to adequately inform the public and clinicians. During a multicenter, randomized controlled trial investigating the efficacy of various dilutions of smallpox vaccine, we observed the appearance of a papulovesicular eruption (focal and generalized) in study volunteers. OBJECTIVE: To characterize the papulovesicular eruptions by clinical, virologic, and histopathological characteristics. DESIGN, SETTING, AND PARTICIPANTS: Prospective case series of papulovesicular eruptions following smallpox vaccination in healthy, vaccinia-naive adult participants compared with noncases conducted from October 2002 to March 2003. Variables potentially related to these eruptions were collected retrospectively through chart review. Eruptions were described based on viral culture, clinical examination, and histopathological evaluation (1 biopsy specimen from 1 case). MAIN OUTCOME MEASURE: Cases of papulovesicular eruptions following vaccination. RESULTS: During the trial, of 148 volunteers (56% women; mean age 23.6 years), 4 participants (2.7%) developed generalized eruptions and 11 (7.4%) noted focal eruptions. Viral cultures of sample lesions were negative for vaccinia. The result of a skin biopsy sample from 1 case of generalized rash revealed suppurative folliculitis without evidence of viral infection. All lesions resolved without scarring. In the cohort, cases and noncases did not show significant differences in terms of sex, in the use of nonsteroidal anti-inflammatory drugs or oral or depo contraceptives, in medication allergies, in the incidence of fever or lymphadenopathy after vaccination, or in the dilution of vaccine received. CONCLUSIONS: Folliculitis is a common and benign eruption observed in vaccinia-naive adult volunteers following smallpox vaccination. This eruption may be seen in volunteers receiving the vaccine in the newly instituted vaccination programs and may be met with heightened anxiety, potentially being confused with generalized vaccinia. This description of folliculitis using clinical, virologic, and histopathological findings should allay these concerns and provide additional insight into this eruption.

Adult↗
PubMed2003

GeneScan reverse transcription-PCR assay for detection of six common respiratory viruses in young children hospitalized with acute respiratory illness.

A reverse transcription-PCR (RT-PCR) assay based on automated fluorescent capillary electrophoresis and GeneScan software analysis was developed to detect six common respiratory viruses in clinical specimens from young children. Assays for human respiratory syncytial virus (HRSV); human parainfluenza viruses 1, 2, and 3 (HPIV1, -2, and -3, respectively); and influenza A and B viruses were incorporated into a single standard assay format. The optimized assay panel was used to test 470 respiratory specimens obtained from 462 children hospitalized with acute respiratory illness that had been previously tested by viral culture (405 specimens) or direct immunofluorescence staining (DIF) (65 specimens). Of 93 specimens positive for respiratory viruses by culture or DIF, 86 (92%) were positive by RT-PCR, including 66 HRSV, 2 HPIV2, 5 HPIV3, 3 influenza A virus, and 10 influenza B virus specimens. An additional 119 respiratory viruses were identified by RT-PCR in 116 patients for whom results were negative by viral isolation or DIF. We conclude that the GeneScan RT-PCR panel can markedly improve detection of acute respiratory virus infections in young children.

Acute Disease↗