Varicella disease after introduction of varicella vaccine in the United States, 1995-2000

Context  Before licensure of varicella vaccine in 1995, varicella was a universal childhood disease in the United States, causing 4 million cases, 11 000 hospitalizations, and 100 deaths every year. Objective  To examine population-based disease surveillance data in 3 communities to document the impact of the varicella vaccination program. Design, Setting, and Subjects  Active surveillance for varicella conducted among the populations of Antelope Valley, Calif; Travis County, Tex; and West Philadelphia, Pa; from January 1, 1995, to December 31, 2000. Reporting sites included child care centers, schools, universities, physicians, public health clinics, hospitals, emergency departments, and households. Main Outcome Measures  Trends in number and rate of varicella cases and hospitalizations; varicella vaccine coverage. Results  From 1995 through 1998, in each surveillance area, the number of verified varicella cases varied from year to year with marked springtime seasonality. In 1999, the number and rates of varicella cases and hospitalizations declined markedly. From 1995 through 2000, in Antelope Valley, Travis County, and West Philadelphia, varicella cases declined 71%, 84%, and 79%, respectively. Cases declined to the greatest extent among children aged 1 to 4 years, but cases declined in all age groups, including infants and adults. In the combined 3 surveillance areas, hospitalizations due to varicella declined from a range of 2.7 to 4.2 per 100 000 population in 1995 through 1998 to 0.6 and 1.5 per 100 000 population in 1999 and 2000, respectively (P = .15). By 2000, vaccine coverage among children aged 19 to 35 months was 82.1%, 73.6%, and 83.8% in Los Angeles County, Texas, and Philadelphia County, respectively. Conclusions  Varicella disease has declined dramatically in surveillance areas with moderate vaccine coverage. Continued implementation of existing vaccine policies should lead to further reductions of varicella disease in these communities and throughout the United States.      

Safety, immunogenicity, and induction of immunologic memory by a serogroup C meningococcal conjugate vaccine in infants: A randomized controlled trial

Context  Neisseria meningitidis is a common cause of meningitis and septicemia in infants worldwide. Whether a meningococcal C conjugate vaccine protects infants against the serogroup C strain is unknown. Objectives  To determine whether a meningococcal C conjugate vaccine is safe and immunogenic and induces immunologic memory in infants. Design  Single-center, double-blind, randomized controlled trial in 1995 and 1996. Setting  Community, Oxfordshire, England. Participants  One hundred eighty-two healthy infants. Interventions  Participants were randomly assigned to receive vaccination with 0.5-mL doses of 1 of 2 lots of meningococcal C conjugate vaccine (groups 1 and 2; n=60 in each group) or a hepatitis B control vaccine (group 3; n=62), administered with routine immunizations at 2, 3, and 4 months of age. Approximately half of each group received meningococcal C conjugate vaccine and half received plain meningococcal polysaccharide vaccine (MPS) at 12 months of age. Main Outcome Measures  Serum antibodies to meningococcal C polysaccharide, assayed by enzyme-linked immunosorbent assay, and serum bactericidal activity (SBA), at 2, 3, 4, 5, 12, and 13 months of age; local and systemic reactions, recorded for 6 days after each vaccination, compared by intervention group. Results  Meningococcal C conjugate vaccine was well tolerated. After 3 doses, children in groups 1 and 2 achieved significantly higher meningococcal C IgG geometric mean concentrations (21 and 17 U/mL, respectively, vs 0.20 U/mL; P<.001) and SBA titers (629 and 420, respectively, vs 4.1; P<.001) than controls. At 12 months, antibody concentrations had decreased in all groups but remained significantly higher in children vaccinated with meningococcal C conjugate vaccine (SBA, 24 and 16 in groups 1 and 2, respectively, vs 4.2 in group 3; P<.001). Following vaccination with MPS at 12 months of age, SBA in the meningococcal C conjugate vaccine group was significantly higher than in controls (SBA, 789 vs 4.5; P<.001). Conclusions  Our data indicate that meningococcal C conjugate vaccine is safe and immunogenic and results in immunologic memory when given with other routinely administered vaccines to infants at 2, 3, and 4 months of age.      

Effectiveness of Haemophilus influenzae type b Conjugate vaccine introduction into routine childhood immunization in Kenya

Context  Haemophilus influenzae type b (Hib) conjugate vaccine is not perceived as a public health priority in Africa because data on Hib disease burden and vaccine effectiveness are scarce. Hib immunization was introduced in Kenyan infants in 2001. Objective  To define invasive Hib disease incidence and Hib vaccine program effectiveness in Kenya. Design, Setting, and Patients  Culture-based surveillance for invasive Hib disease at Kilifi District Hospital from 2000 through 2005 was linked to demographic surveillance of 38 000 children younger than 5 years in Kilifi District, Kenya. Human immunodeficiency virus (HIV) infection and Hib vaccination status were determined for children with Hib disease admitted 2002-2005. Interventions  Introduction of conjugate Hib vaccine within the routine childhood immunization program at ages 6, 10, and 14 weeks beginning November 2001. Main Outcome Measures  Incidence of culture-proven Hib invasive disease before and after vaccine introduction and vaccine program effectiveness. Results  Prior to vaccine introduction, the median age of children with Hib was 8 months; case fatality was 23%. Among children younger than 5 years, the annual incidence of invasive Hib disease 1 year before and 1 and 3 years after vaccine introduction was 66, 47, and 7.6 per 100 000, respectively. For children younger than 2 years, incidence was 119, 82, and 16 per 100 000, respectively. In 2004-2005, vaccine effectiveness was 88% (95% confidence interval, 73%-96%) among children younger than 5 years and 87% (95% confidence interval, 66%-96%) among children younger than 2 years. Of 53 children with Hib admitted during 2002-2005, 29 (55%) were age-ineligible to have received vaccine, 12 (23%) had not been vaccinated despite being eligible, and 12 (23%) had received 2 or more doses of vaccine (2 were HIV positive). Conclusions  In Kenya, introduction of Hib vaccine into the routine childhood immunization program reduced Hib disease incidence among children younger than 5 years to 12% of its baseline level. This impact was not observed until the third year after vaccine introduction.      

Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial

Context  Acute otitis media (AOM) frequently complicates influenza infection. Previous studies have found influenza vaccine effective in reducing the occurrence of AOM in children mainly older than 2 years. Objective  To evaluate the effectiveness of inactivated influenza vaccine in preventing AOM in children aged 6 to 24 months. Design, Setting, and Patients  Randomized, double-blind, placebo-controlled trial of 786 children aged 6 to 24 months enrolled at Children's Hospital of Pittsburgh before the 1999-2000 (411 children) and 2000-2001 (375 children) respiratory seasons (defined as December 1 through March 31 of the respective following year). Children received influenza vaccine or placebo in a 2:1 ratio. The first cohort was observed for 1 year and the second cohort until the end of the ensuing respiratory season. Intervention  Two doses (0.25 mL each) of inactivated trivalent subvirion influenza vaccine or placebo were administered intramuscularly approximately 4 weeks apart. Main Outcome Measures  Proportion of children who developed AOM, monthly occurrence rate of AOM, estimated proportion of time with middle ear effusion, and utilization of selected health care and related resources. Results  Of the 66 children in the vaccine group from whom serum samples were collected, seroconversion against strains in the vaccine formulations developed in 88.6% to 96.8%, depending on the specific strain. The efficacy of the vaccine against culture-confirmed influenza was 66% (95% confidence interval [CI], 34%-82%) in 1999-2000 and -7% (95% CI, -247% to 67%) in 2000-2001; however, influenza attack rates differed between these 2 periods (in the placebo group, 15.9% and 3.3%, respectively). Compared with placebo, influenza vaccine did not reduce the proportion of children who had at least 1 episode of AOM during the respiratory season (in the first cohort: vaccine, 49.2% vs placebo, 52.2%; P = .56 ]; in the second cohort: vaccine, 55.8% vs placebo, 48.3%; P = .17). The vaccine also did not reduce the monthly rate of AOM; the estimated proportion of time with middle ear effusion; or the utilization of selected health care and related resources. There were also no differences between the vaccine and placebo groups regarding any of these outcomes during peak influenza periods. The vaccines administered to both cohorts of children were well tolerated. Conclusion  Administration of inactivated trivalent influenza vaccine to children aged 6 to 24 months did not reduce their burden of AOM or their utilization of selected health care and related resources.      

Response to smallpox vaccine in persons immunized in the distant past

Context  There is renewed interest in use of smallpox vaccine due to the potential for a bioterrorist attack. This would involve vaccinating health care workers who were previously vaccinated. Objective  To evaluate the use of diluted vaccinia virus in vaccination of previously vaccinated (non-naive) participants. Design, Setting, and Participants  Eighty non-naive participants, aged 32 to 60 years, were randomized in a single-blinded study to receive either undiluted or diluted (1:3.2, 1:10, or 1:32) doses of smallpox vaccine. A comparison group, aged 18 to 31 years, of 10 vaccinia-naive participants received undiluted vaccine. Participants were enrolled between April 1 and May 15, 2002, at the National Institute of Allergy and Infectious Diseases Vaccine and Treatment Evaluation Unit at Saint Louis University, St Louis, Mo. Intervention  Smallpox vaccine was administered by scarification using 15 skin punctures in the deltoid region of the arm. Main Outcome Measures  Presence of a major reaction, defined as a vesicular or pustular lesion or area of palpable induration surrounding a central lesion following vaccination, and measures of viral shedding and antibody titers. Results  Initial vaccination resulted in a major reaction in 64 of 80 non-naive participants. Ninety-five percent of non-naive participants had major reactions in the undiluted group, 90% in the 1:3.2 dilution group, 81% in the 1:10 dilution group, and 52.6% in the 1:32 dilution group. All (n = 10) of the vaccinia-naive participants had major reactions. Compared with vaccinia-naive participants, non-naive participants had significantly smaller skin lesions (P = .04) and significantly less incidence of fever (P = .02). Preexisting antibody was present in 76 of 80 non-naive participants. Antibody responses were significantly higher and occurred more rapidly in the non-naive participants compared with the vaccinia-naive participants (P = .002 for day 28 and P = .003 for 6 months). Vaccinia-naive participants shed virus from the vaccination site 2 to 6 days longer and had significantly higher peak mean viral titers when compared with the non-naive participants (P = .002). Conclusions  Previously vaccinated persons can be successfully revaccinated with diluted (≤1:10) smallpox vaccine. Fewer adverse reactions were observed in this study of non-naive participants when compared with events in vaccinia-naive participants, which may be due to immunologic memory.      

Vaccination success rate and reaction profile with diluted and undiluted smallpox vaccine: a randomized controlled trial

Context  Additional smallpox vaccine doses are needed to augment current US national stockpile. Aventis Pasteur smallpox vaccine (APSV), initially manufactured in the 1950s from the New York Board of Health vaccinia strain in a frozen preparation, appears as effective as lyophilized vaccine but the effectiveness of diluted doses of APSV is unclear. Objective  To compare the vaccination success rate and the reaction profile of various APSV dilutions. Design, Setting, and Participants  A double-blind, randomized controlled trial of 340 healthy vaccinia-naive adults aged 18 to 32 years from 3 academic medical centers who were vaccinated with 1 of 3 strengths of APSV dilutions (undiluted, 1:5, and 1:10) between October 9, 2002, and February 24, 2003. Volunteers were followed up every 3 to 5 days until the vaccination site healed for bandage changes, vaccine response assessment, and adverse event evaluation, followed by 1- and 2-month clinic evaluations and 6-month telephone interview. Main Outcome Measures  Successful vaccination, defined by presence of a vesicle or pustule at the inoculation site 6 to 11 days postvaccination, and local and systemic reactions to vaccination. Results  A total of 340 volunteers were vaccinated (vaccine dose: undiluted, n = 113; 1:5 dilution, n = 114; and 1:10 dilution, n = 113). Following vaccination, 99.4% (95% confidence interval [CI], 97.9%-99.9%) of all volunteers had successful vaccinations. Success rates did not differ between the dilution groups (undiluted, 100.0%; 95% CI, 96.8%-100.0%; 1:5 dilution, 98.2%; 95% CI, 93.8%-99.8%; 1:10 dilution, 100.0% 95% CI, 96.8%-100.0%; P = .33). Overall, 99.7% of volunteers reported at least 1 local symptom at the vaccination site, and 61.8% had axillary lymphadenopathy, 15.0% developed satellite lesions, and 7.6% developed a rash away from the vaccination site. Fever developed in 21.5%. No differences were noted in local or systemic reactions between the 3 dilution groups (P>.05 for each comparison). A total of 25% of volunteers missed scheduled duties due to vaccine-related symptoms. Conclusions  Even at diluted doses, APSV is an effective smallpox vaccine, allowing for expansion of the current stockpile. However, reactogenicity was not reduced with dilution of the vaccine and, as with other smallpox vaccines, may impair daily activities.      

Invasive meningococcal disease in adolescents and young adults

Context  Incidence of invasive meningococcal disease has increased recently in persons aged 15 through 24 years. Objective  To characterize meningococcal infection in adolescents and young adults in Maryland during the 1990s. Design and Setting  Population-based surveillance study for meningococcal disease from January 1, 1990, through December 31, 1999, in Maryland. Patients  Maryland residents diagnosed as having invasive meningococcal disease. Main Outcome Measure  Invasive meningococcal infection. Results  Of 295 total cases, 71 (24.1%) occurred among persons aged 15 through 24 years. Sixteen (22.5%) of these cases were fatal. The annual incidence rate increased from 0.9 to 2.1 cases per 100 000 among 15 through 24 year olds (P = .01). The proportion of all disease increased from 16.0% to 28.9% (P = .03). The incidence and proportion of cases subsequently decreased to 1.0 and 16.4% in 1998 through 1999, respectively. Infection in 15 through 24 year olds was more likely to be fatal than infection in those younger than age 15 years (22.5% vs 4.6%; P = .001). Infection in 15 through 24 year olds, compared with those aged 25 years or older, was more likely to be associated with male sex (66.2% vs 34.8%; P<.001) and serogroup C infection (46.9% vs 20.2%; P<.001), respectively. Infections were potentially preventable with the licensed meningococcal vaccine in 82.8% of 15 through 24 year olds, 68.1% of those younger than 15 years, and 76.8% of adults aged 25 years or older. Conclusions  Incidence of meningococcal infection in 15 through 24 year olds in Maryland increased and then declined during the 1990s. Infection in this age group was associated with an unusually high case-fatality ratio, and the vast majority of cases were potentially vaccine preventable.      

Inpatient computer-based standing orders vs physician reminders to increase influenza and pneumococcal vaccination rates: a randomized trial

Context  Computerized reminder systems increase influenza and pneumococcal vaccination rates, but computerized standing order systems have not been previously described or evaluated. Objective  To determine the effects of computerized physician standing orders compared with physician reminders on inpatient vaccination rates. Design, Setting, and Patients  Randomized trial of 3777 general medicine patients discharged from 1 of 6 study wards during a 14-month period (November 1, 1998, through December 31, 1999) composed of 2 overlapping influenza seasons at an urban public teaching hospital. Interventions  The hospital’s computerized physician order entry system identified inpatients eligible for influenza and pneumococcal vaccination. For patients with standing orders, the system automatically produced vaccine orders directed to nurses at the time of patient discharge. For patients with reminders, the computer system provided reminders to physicians that included vaccine orders during routine order entry sessions. Main Outcome Measure  Vaccine administration. Results  During the approximately 6 months of the influenza season, 50% of all hospitalized patients were identified as eligible for influenza vaccination. Twenty-two percent of patients hospitalized during the entire 14 months of the study were found eligible for pneumococcal vaccination. Patients with standing orders received an influenza vaccine significantly more often (42%) than those patients with reminders (30%) (P <.001). Patients with standing orders received a pneumococcal vaccine significantly more often (51%) than those with reminders (31%) (P <.001). Conclusions  Computerized standing orders were more effective than computerized reminders for increasing both influenza and pneumococcal vaccine administration. Our findings suggest that computerized standing orders should be used more widely for this purpose.      

Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial

Context  The scarcity of data addressing the health effects of popular diets is an important public health concern, especially since patients and physicians are interested in using popular diets as individualized eating strategies for disease prevention. Objective  To assess adherence rates and the effectiveness of 4 popular diets (Atkins, Zone, Weight Watchers, and Ornish) for weight loss and cardiac risk factor reduction. Design, Setting, and Participants  A single-center randomized trial at an academic medical center in Boston, Mass, of overweight or obese (body mass index: mean, 35; range, 27-42) adults aged 22 to 72 years with known hypertension, dyslipidemia, or fasting hyperglycemia. Participants were enrolled starting July 18, 2000, and randomized to 4 popular diet groups until January 24, 2002. Intervention  A total of 160 participants were randomly assigned to either Atkins (carbohydrate restriction, n=40), Zone (macronutrient balance, n=40), Weight Watchers (calorie restriction, n=40), or Ornish (fat restriction, n=40) diet groups. After 2 months of maximum effort, participants selected their own levels of dietary adherence. Main Outcome Measures  One-year changes in baseline weight and cardiac risk factors, and self-selected dietary adherence rates per self-report. Results  Assuming no change from baseline for participants who discontinued the study, mean (SD) weight loss at 1 year was 2.1 (4.8) kg for Atkins (21 [53%] of 40 participants completed, P = .009), 3.2 (6.0) kg for Zone (26 [65%] of 40 completed, P = .002), 3.0 (4.9) kg for Weight Watchers (26 [65%] of 40 completed, P < .001), and 3.3 (7.3) kg for Ornish (20 [50%] of 40 completed, P = .007). Greater effects were observed in study completers. Each diet significantly reduced the low-density lipoprotein/high-density lipoprotein (HDL) cholesterol ratio by approximately 10% (all P<.05), with no significant effects on blood pressure or glucose at 1 year. Amount of weight loss was associated with self-reported dietary adherence level (r = 0.60; P<.001) but not with diet type (r = 0.07; P = .40). For each diet, decreasing levels of total/HDL cholesterol, C-reactive protein, and insulin were significantly associated with weight loss (mean r = 0.36, 0.37, and 0.39, respectively) with no significant difference between diets (P = .48, P = .57, P = .31, respectively). Conclusions  Each popular diet modestly reduced body weight and several cardiac risk factors at 1 year. Overall dietary adherence rates were low, although increased adherence was associated with greater weight loss and cardiac risk factor reductions for each diet group.      

Effectiveness of influenza vaccine in health care professionals: a randomized trial

Context  Data are limited and conflicting regarding the effectiveness of influenza vaccine in health care professionals. Objective  To determine the effectiveness of trivalent influenza vaccine in reducing infection, illness, and absence from work in young, healthy health care professionals. Design  Randomized, prospective, double-blind, controlled trial over 3 consecutive years, from 1992-1993 to 1994-1995. Setting  Two large teaching hospitals in Baltimore, Md. Participants  Two hundred sixty-four hospital-based health care professionals without chronic medical problems were recruited; 49 participated for 2 seasons; 24 participated for 3 seasons. The mean age was 28.4 years, 75% were resident physicians, and 57% were women. Intervention  Participants were randomly assigned to receive either an influenza vaccine or a control (meningococcal vaccine, pneumococcal vaccine, or placebo). Serum samples for antibody assays were collected at the time of vaccination, 1 month after vaccination, and at the end of the influenza season. Active weekly surveillance for illness was conducted during each influenza epidemic period. Main Outcome Measures  Serologically defined influenza infection (4-fold increase in hemagglutination-inhibiting antibodies), days of febrile respiratory illness, and days absent from work. Results  We conducted 359 person-winters of serologic surveillance (99.4% follow-up) and 4746 person-weeks of illness surveillance (100% follow-up). Twenty-four (13.4%) of 179 control subjects and 3 (1.7%) of 180 influenza vaccine recipients had serologic evidence of influenza type A or B infection during the study period. Vaccine efficacy against serologically defined infection was 88% for influenza A (95% confidence interval [CI], 47%-97%; P=.001) and 89% for influenza B (95% CI, 14%-99%; P=.03). Among influenza vaccinees, cumulative days of reported febrile respiratory illness were 28.7 per 100 subjects compared with 40.6 per 100 subjects in controls (P=.57) and days of absence were 9.9 per 100 subjects vs 21.1 per 100 subjects in controls (P=.41). Conclusions  Influenza vaccine is effective in preventing infection by influenza A and B in health care professionals and may reduce reported days of work absence and febrile respiratory illness. These data support a policy of annual influenza vaccination of health care professionals.      

Immunogenicity and safety of a combination pneumococcal-meningococcal vaccine in infants: a randomized controlled trial

Context  The success of conjugate vaccines in decreasing invasive disease due to Streptococcus pneumoniae and group C Neisseria meningitidis has placed pressure on crowded infant immunization schedules, making development of combination vaccines a priority. Objective  To determine the safety and immunogenicity of a combination 9-valent pneumococcal–group C meningococcal conjugate candidate vaccine (Pnc9-MenC) administered as part of the routine UK infant immunization schedule at ages 2, 3, and 4 months. Design, Setting, and Participants  Phase 2 randomized controlled trial conducted from August 2000 to January 2002 and enrolling 240 healthy infants aged 7 to 11 weeks from 2 UK centers, with home follow-up visits at ages 2, 3, 4, and 5 months. Intervention  Pnc9-MenC (n = 120) or monovalent group C meningococcal conjugate vaccine (MenC) (n = 120) administered in addition to routine immunizations (diphtheria and tetanus toxoids and whole-cell pertussis [DTwP], Haemophilus influenzae type b [Hib] polyribosylribitol phosphate-tetanus toxoid protein conjugate, oral polio vaccine). Main Outcome Measures  Group C meningococcal immunogenicity measured by serum bactericidal titer (SBT) 1 month following the third dose; rates of postimmunization reactions. Results  MenC component immunogenicity was reduced in the Pnc9-MenC vs the MenC group (geometric mean SBT, 179 [95% confidence interval {CI}, 133-243] vs 808 [95% CI, 630-1037], respectively; P<.001). The proportion with group C meningococcal SBT greater than 1:8 was lower in the Pnc9-MenC vs the MenC group (95% vs 100%, P = .05). The geometric mean concentration of antibodies to concomitantly administered Hib vaccine was reduced in the Pnc9-MenC vs the MenC group (2.11 [95% CI, 1.57-2.84] µg/mL vs 3.36 [95% CI, 2.57-4.39] µg/mL; P = .02), as were antibodies against diphtheria (0.74 [95% CI, 0.63-0.87] µg/mL vs 1.47 [95% CI, 1.28-1.69] µg/mL; P<.001). Pnc9-MenC was immunogenic for each of 9 contained pneumococcal serotypes, with responses greater than 0.35 µg/mL observed in more than 88% of infants. Increased irritability and decreased activity were observed after the third dose in the Pnc9-MenC group. Conclusions  Pnc9-MenC combination vaccine administered to infants at ages 2, 3, and 4 months demonstrated reduced group C meningococcal immunogenicity compared with MenC vaccine. The immunogenicity of concomitantly administered Hib and DTwP vaccines was also diminished. The Pnc9-MenC vaccine was safe and immunogenic for all contained pneumococcal serotypes. The reduced MenC immunogenicity may limit the development of the Pnc9-MenC vaccine.      

Reducing suicidal ideation and depressive symptoms in depressed older primary care patients: a randomized controlled trial

Context  Suicide rates are highest in late life; the majority of older adults who die by suicide have seen a primary care physician in preceding months. Depression is the strongest risk factor for late-life suicide and for suicide's precursor, suicidal ideation. Objective  To determine the effect of a primary care intervention on suicidal ideation and depression in older patients. Design and Setting  Randomized controlled trial known as PROSPECT (Prevention of Suicide in Primary Care Elderly: Collaborative Trial) with patient recruitment from 20 primary care practices in New York City, Philadelphia, and Pittsburgh regions, May 1999 through August 2001. Participants  Two-stage, age-stratified (60-74, =" BORDER="0">75 years) depression screening of randomly sampled patients; enrollment included patients who screened positive and a random sample of screened negative patients. This analysis included patients with a depression diagnosis (N = 598). Intervention  Treatment guidelines tailored for the elderly with care management compared with usual care. Main Outcome Measures  Assessment of suicidal ideation and depression severity at baseline, 4 months, 8 months, and 12 months. Results  Rates of suicidal ideation declined faster (P = .01) in intervention patients compared with usual care patients; at 4 months, in the intervention group, raw rates of suicidal ideation declined 12.9% points (29.4% to 16.5%) compared with 3.0% points (20.1% to 17.1% in usual care [P = .01]). Among patients reporting suicidal ideation, resolution of ideation was faster among intervention patients (P = .03); differences peaked at 8 months (70.7% vs 43.9% resolution; P = .005). Intervention patients had a more favorable course of depression in both degree and speed of symptom reduction; group difference peaked at 4 months. The effects on depression were not significant among patients with minor depression unless suicidal ideation was present. Conclusions  Evidence of the intervention's effectiveness in community-based primary care with a heterogeneous sample of depressed patients introduces new challenges related to its sustainability and dissemination. The intervention's effectiveness in reducing suicidal ideation, regardless of depression severity, reinforces its role as a prevention strategy to reduce risk factors for suicide in late life.      

Contagiousness of varicella in vaccinated cases: a household contact study

Context  Limited data are available on the contagiousness of vaccinated varicella cases. Objectives  To describe secondary attack rates within households according to disease history and vaccination status of the primary case and household contacts and to estimate varicella vaccine effectiveness. Design, Setting, and Patients  Population-based, active varicella surveillance project in a community of approximately 320 000 in Los Angeles County, California, during 1997 and 2001. Varicella cases were reported by child care centers, private and public schools, and health care clinicians and were investigated to collect demographic, clinical, medical, and vaccination data. Information on household contacts' age, varicella history, and vaccination status was collected. Main Outcome Measures  Varicella secondary attack rate among household contacts; vaccine effectiveness using secondary attack rates in unvaccinated and vaccinated children and adolescents. Results  A total of 6316 varicella cases were reported. Among children and adolescents aged 1 to 14 years, secondary attack rates varied according to age and by disease and vaccination status of the primary case and exposed household contacts. Among contacts aged 1 to 14 years exposed to unvaccinated cases, the secondary attack rate was 71.5% if they were unvaccinated and 15.1% if they were vaccinated (risk ratio [RR], 0.21; 95% confidence interval [CI], 0.15-0.30). Overall, vaccinated cases were half as contagious as unvaccinated cases. However, vaccinated cases with 50 lesions or more were similarly contagious as unvaccinated cases whereas those with fewer than 50 lesions were only one third as contagious (secondary attack rate, 23.4%; RR, 0.32 [95% CI, 0.19-0.53]). Vaccine effectiveness for prevention of all disease was 78.9% (95% CI, 69.7%-85.3%); moderate disease, 92% (50-500 lesions) and 100% (clinician visit); and severe disease, 100%. Conclusions  Under conditions of intense exposure, varicella vaccine was highly effective in preventing moderate and severe disease and about 80% effective in preventing all disease. Breakthrough varicella cases in household settings were half as contagious as unvaccinated persons with varicella, although contagiousness varied with numbers of lesions.      

Hepatitis B vaccination among children in inner-city public housing, 1991-1997

Context  In 1991, the Advisory Committee on Immunization Practices recommended universal vaccination of infants against hepatitis B virus (HBV), with series initiation within days of birth. Objective  To determine HBV vaccine coverage in a low-income urban population and to examine whether HBV immunization within the first month of life affects subsequent vaccine receipt. Design  Cohort study based on immunization records collected in the Pediatric Immunization Program. Setting  Large public housing development in Chicago, Ill. Participants  All 1143 children who were born between 1991 and 1997 and enrolled between 1993 and mid-1998, with follow-up to age 35 months. Main Outcome Measures  On-time vaccine receipt of HBV vaccine doses, diphtheria-tetanus-pertussis vaccine (DTP) dose 1, and the 4:3:1 series (4 doses of DTP vaccine, 3 doses of poliomyelitis vaccine, and 1 dose of measles-containing vaccine), analyzed by year. Results  On-time HBV vaccination increased quickly following new guidelines and reached a plateau of about 50% coverage for those born in or after 1995. Since 1994, more children (64%) received the first HBV vaccine dose on time than any other vaccine. Children who received a dose of HBV vaccine during their first month of life were more likely to receive the first DTP vaccine dose on time (60.1%) than those who did not get an HBV vaccine dose during the first month (36.4%; ² = 53.7; P<.001). Children who received the first HBV vaccine dose during their first month were more likely than those receiving it at age 1 to 2 months to complete 3 HBV doses by 19 months (70.6% vs 51.1%; ² = 11.6; P = .001) and to complete the 4:3:1 series by age 19 months (49.8% vs 37.9%; ² = 4.0; P = .05). Conclusions  In this inner-city population, HBV vaccine has been received at rates similar to those of other vaccines within 3 years of issuance of new recommendations. Of note, immunization with HBV vaccine at birth was associated with timely receipt of other vaccines and, therefore, may have the potential to increase vaccination among groups less likely to be up-to-date on early childhood vaccines.      

Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among young women with preexisting infection: a randomized trial

Context  Viruslike particle human papillomavirus (HPV) vaccines were designed to prevent HPV infection and development of cervical precancers and cancer. Women with oncogenic HPV infections might consider vaccination as therapy. Objective  To determine whether vaccination against HPV types 16 and 18 increases the rate of viral clearance in women already infected with HPV. Design and Setting  Phase 3, masked, community-based randomized trial conducted in 2 provinces of Costa Rica. Participants  A total of 2189 women aged 18 to 25 years who were recruited between June 2004 and December 2005. Participants were positive for HPV DNA at enrollment, had at least 6 months of follow-up, and had follow-up HPV DNA results. Intervention  Participants were randomly assigned to receive 3 doses of a bivalent HPV-16/18 L1 protein viruslike particle AS04 candidate vaccine (n = 1088) or a control hepatitis A vaccine (n = 1101) over 6 months. Main Outcome Measures  Presence of HPV DNA was determined in cervical specimins by a molecular hybridization assay using chemiluminescence with HPV RNA probes and by polymerase chain reaction using SPF10 primers and a line probe assay detection system before vaccination and by polymerase chain reaction after vaccination. We compared rates of type-specific viral clearance using generalized estimating equations methods at the 6-month visit (after 2 doses) and 12-month visit (after 3 doses) in the 2 study groups. Results  There was no evidence of increased viral clearance at 6 or 12 months in the group who received HPV vaccine compared with the control group. Clearance rates for HPV-16/18 infections at 6 months were 33.4% (82/248) in the HPV vaccine group and 31.6% (95/298) in the control group (vaccine efficacy for viral clearance, 2.5%; 95% confidence interval, –9.8% to 13.5%). Human papillomavirus 16/18 clearance rates at 12 months were 48.8% (86/177) in the HPV vaccine group and 49.8% (110/220) in the control group (vaccine efficacy for viral clearance, –2.0%; 95% confidence interval, –24.3% to 16.3%). There was no evidence of a therapeutic effect for other oncogenic or nononcogenic HPV categories, among women receiving all vaccine doses, among women with single infections, or among women stratified by the following entry variables: HPV-16/18 serology, cytologic results, HPV DNA viral load, time since sexual debut, Chlamydia trachomatis or Neisseria gonorrhoeae infection, hormonal contraceptive use, or smoking. Conclusion  In women positive for HPV DNA, HPV-16/18 vaccination does not accelerate clearance of the virus and should not be used to treat prevalent infections. Trial Registration  clinicaltrials.gov Identifier: NCT00128661      

Invasive pneumococcal disease caused by nonvaccine serotypes among alaska native children with high levels of 7-valent pneumococcal conjugate vaccine coverage

Rosalyn J. Singleton, MD, MPH; Thomas W. Hennessy, MD, MPH; Lisa R. Bulkow, MS; Laura L. Hammitt, MD; Tammy Zulz, BS; Debby A. Hurlburt, RN; Jay C. Butler, MD; Karen Rudolph, PhD; Alan Parkinson, PhD

JAMA. 2007;297:1784-1792.

Context  With routine childhood vaccination using heptavalent pneumococcal conjugate vaccine, one concern has been the potential for emergence and expansion of replacement disease caused by serotypes not contained in the heptavalent conjugate vaccine.

Objective  To determine whether replacement disease is associated with the overall decline in invasive pneumococcal disease among Alaska Native children.

Design, Setting, and Patients  Alaska statewide longitudinal population-based laboratory surveillance of invasive Streptococcus pneumoniae infections from January 1, 1995, through December 31, 2006.

Main Outcome Measures  Incidence and types of pneumococcal disease in children younger than 2 years.

Results  In the first 3 years after introduction of routine vaccination with heptavalent pneumococcal conjugate vaccine, overall invasive pneumococcal disease decreased 67% in Alaska Native children younger than 2 years (from 403.2 per 100 000 in 1995-2000 to 134.3 per 100 000 per year in 2001-2003, P<.001). However, between 2001-2003 and 2004-2006, there was an 82% increase in invasive disease in Alaska Native children younger than 2 years to 244.6/100 000 (P = .02). Since 2004, the invasive pneumococcal disease rate caused by nonvaccine serotypes has increased 140% compared with the prevaccine period (from 95.1 per 100 000 in 1995-2000 to 228.6 in 2004-2006, P = .001). During the same period, there was a 96% decrease in heptavalent vaccine serotype disease. Serotype 19A accounted for 28.3% of invasive pneumococcal disease among Alaska children younger than 2 years during 2004-2006. There was no significant increase in nonvaccine disease in non–Native Alaska children younger than 2 years.

Conclusions  Alaska Native children are experiencing replacement invasive pneumococcal disease with serotypes not covered by heptavalent pneumococcal conjugate vaccine. The demonstration of replacement invasive pneumococcal disease emphasizes the importance of ongoing surveillance and development of expanded valency vaccines.

     

Trends in suicide ideation, plans, gestures, and attempts in the United States, 1990-1992 to 2001-2003

Context  Little is known about trends in suicidal ideation, plans, gestures, or attempts or about their treatment. Such data are needed to guide and evaluate policies to reduce suicide-related behaviors. Objective  To analyze nationally representative trend data on suicidal ideation, plans, gestures, attempts, and their treatment. Design, Setting, and Participants  Data came from the 1990-1992 National Comorbidity Survey and the 2001-2003 National Comorbidity Survey Replication. These surveys asked identical questions to 9708 people aged 18 to 54 years about the past year’s occurrence of suicidal ideation, plans, gestures, attempts, and treatment. Trends were evaluated by using pooled logistic regression analysis. Face-to-face interviews were administered in the homes of respondents, who were nationally representative samples of US English-speaking residents. Main Outcome Measure  Self-reports about suicide-related behaviors and treatment in the year before interview. Results  No significant changes occurred between 1990-1992 and 2001-2003 in suicidal ideation (2.8% vs 3.3%; P = .43), plans (0.7% vs 1.0%; P = .15), gestures (0.3% vs 0.2%; P = .24), or attempts (0.4%-0.6%; P = .45), whereas conditional prevalence of plans among ideators increased significantly (from 19.6% to 28.6%; P = .04), and conditional prevalence of gestures among planners decreased significantly (from 21.4% to 6.4%; P = .003). Treatment increased dramatically among ideators who made a gesture (40.3% vs 92.8%) and among ideators who made an attempt (49.6% vs 79.0%). Conclusions  Despite a dramatic increase in treatment, no significant decrease occurred in suicidal thoughts, plans, gestures, or attempts in the United States during the 1990s. Continued efforts are needed to increase outreach to untreated individuals with suicidal ideation before the occurrence of attempts and to improve treatment effectiveness for such cases.      

Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents

Context  Traditionally, stent thrombosis has been regarded as a complication of percutaneous coronary interventions during the first 30 postprocedural days. However, delayed endothelialization associated with the implantation of drug-eluting stents may extend the risk of thrombosis beyond 30 days. Data are limited regarding the risks and the impact of this phenomenon outside clinical trials. Objective  To evaluate the incidence, predictors, and clinical outcome of stent thrombosis after implantation of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice. Design, Setting, and Patients  Prospective observational cohort study conducted at 1 academic hospital and 2 community hospitals in Germany and Italy. A total of 2229 consecutive patients underwent successful implantation of sirolimus-eluting (1062 patients, 1996 lesions, 2272 stents) or paclitaxel-eluting (1167 patients, 1801 lesions, 2223 stents) stents between April 2002 and January 2004. Interventions  Implantation of a drug-eluting stent (sirolimus or paclitaxel). All patients were pretreated with ticlopidine or clopidogrel and aspirin. Aspirin was continued indefinitely and clopidogrel or ticlopidine for at least 3 months after sirolimus-eluting and for at least 6 months after paclitaxel-eluting stent implantation. Main Outcome Measures  Subacute thrombosis (from procedure end through 30 days), late thrombosis (>30 days), and cumulative stent thrombosis. Results  At 9-month follow-up, 29 patients (1.3%) had stent thrombosis (9 [0.8%] with sirolimus and 20 [1.7%] with paclitaxel; P = .09). Fourteen patients had subacute thrombosis (0.6%) and 15 patients had late thrombosis (0.7%). Among these 29 patients, 13 died (case fatality rate, 45%). Independent predictors of stent thrombosis were premature antiplatelet therapy discontinuation (hazard ratio [HR],  89.78; 95% CI, 29.90-269.60; P<.001), renal failure (HR,  6.49; 95% CI, 2.60-16.15; P<.001), bifurcation lesions (HR,  6.42; 95% CI, 2.93-14.07; P<.001), diabetes (HR,  3.71; 95% CI, 1.74-7.89; P = .001), and a lower ejection fraction (HR,  1.09; 95% CI, 1.05-1.36; P<.001 for each 10% decrease). Conclusions  The cumulative incidence of stent thrombosis 9 months after successful drug-eluting stent implantation in consecutive "real-world" patients was substantially higher than the rate reported in clinical trials. Premature antiplatelet therapy discontinuation, renal failure, bifurcation lesions, diabetes, and low ejection fraction were identified as predictors of thrombotic events.      

Effectiveness of a mass immunization campaign using serogroup C meningococcal conjugate vaccine

Context  Meningococcal polysaccharide vaccines are of limited effectiveness. New protein-polysaccharide conjugate vaccines have yet to be evaluated in field conditions. Objective  To assess the effectiveness of a serogroup C conjugate meningococcal vaccine in an outbreak setting. Design, Setting, and Participants  Population-based observational study of cases of invasive serogroup C meningococcal disease from 1996 through 2002 in Quebec identified from the provincial registry of notifiable diseases and from the provincial reference laboratory. In 2001, a mass immunization campaign with a conjugate vaccine was conducted to control an emerging epidemic. The number of vaccinated individuals was extracted from meningococcal immunization registries. Main Outcome Measures  Incidence of invasive meningococcal disease before and 1 year after the campaign in vaccinated and unvaccinated individuals. Results  Vaccination coverage of those 2 months to 20 years was 82.1%. After the campaign, the number of cases of serogroup C disease decreased from 58 in 2001 to 27 in 2002, and the incidence from 7.8 per million to 3.6 per million. Vaccine effectiveness was found to be 96.8% (95% confidence interval, 75.0%-99.9%). There was no observed increase in the incidence of the other serogroups. Conclusion  The new conjugate vaccine was effective in controlling an emerging epidemic of serogroup C meningococcal disease, as well as providing short-term protection across a wide age range.