Impact of childhood vaccination on racial disparities in invasive Streptococcus pneumoniae infections

Context  Historically, incidence of pneumococcal disease in the United States has been higher among blacks than among whites. Following recommendation of a new 7-valent pneumococcal conjugate vaccine for children in October 2000, the incidence of invasive pneumococcal disease has declined dramatically, but the impact of vaccination on racial disparities in incidence of pneumococcal disease is unknown. Objective  To assess the effect of conjugate vaccine introduction on rates of pneumococcal disease among whites and blacks in the United States. Design, Setting, and Patients  Analysis of data from the Active Bacterial Core Surveillance (ABCs)/Emerging Infections Program Network, an active, population-based surveillance system in 7 states. Patients were 15 923 persons with invasive pneumococcal disease occurring between January 1, 1998, and December 31, 2002. Main Outcome Measures  Age- and race-specific pneumococcal disease incidence rates (cases per 100 000 persons), rate ratios, and rate differences. Results  Between 1998 and 2002, annual incidence rates for invasive pneumococcal disease decreased from 19.0 to 12.1 cases per 100 000 among whites and from 54.9 to 26.5 among blacks. Due to these declines, 14 730 fewer cases occurred among whites and 8780 fewer cases occurred among blacks in the United States in 2002, compared with 2 prevaccine years, 1998 and 1999. Before vaccine introduction, incidence among blacks was 2.9 times higher than among whites (95% confidence interval [CI], 2.7-3.0); in 2002, the black-white rate ratio had been reduced to 2.2 (95% CI, 2.0-2.4). Incidence among black children younger than 2 years went from being 3.3 times higher (95% CI, 3.0-3.7) than among white children in the prevaccine period to 1.6 times higher (95% CI, 1.1-2.2) in 2002. By 2002, 74% of white children and 68% of black children aged 19 to 35 months in the 7 states had received at least 1 dose of pneumococcal conjugate vaccine; 43% of white and 39% of black children received 3 or more doses. Conclusion  Although blacks remain at higher risk of invasive pneumococcal disease, introduction of childhood pneumococcal vaccination has reduced the racial disparity in incidence of pneumococcal disease.      

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.

     

Incidence of hepatitis A in Israel following universal immunization of toddlers

Context  In Israel, the mean annual incidence of hepatitis A disease was 50.4 per 100 000 during 1993-1998. A 2-dose universal hepatitis A immunization program aimed at children aged 18 and 24 months (without a catch-up campaign) was started in 1999. Objective  To observe the impact of toddlers-only universal vaccination on hepatitis A virus disease in Israel. Design and Setting  Ongoing passive national surveillance of hepatitis A cases in Israel has been conducted since 1993 by the Ministry of Health. An active surveillance program in the Jerusalem district in 1999-2003 provided validation for the passive program. Main Outcome Measure  Incidence of reported hepatitis A disease, 1993-2004. Results  Overall vaccine coverage in Israel in 2001-2002 was 90% for the first dose and 85% for the second dose. A decline in disease rates was observed before 1999 among the Jewish but not the non-Jewish population. After initiation of the program, a sharp decrease in disease rates was observed in both populations. The annual incidence of 2.2 to 2.5 per 100 000 during 2002-2004 represents a 95% or greater reduction for each year with respect to the mean incidence during 1993-1998 (P<.001). For children aged 1 through 4 years, a 98.2% reduction in disease was observed in 2002-2004, compared with the prevaccination period (P<.001). However, a sharp decline was also observed in all other age groups (84.3% [<1 year], 96.5% [5-9 years], 95.2% [10-14 years], 91.3% [15-44 years], 90.6% [45-64 years], and 77.3% [65 years]). Among the Jewish population in the Jerusalem district, in whom the active surveillance program was successfully conducted, a more than 90% reduction of disease was demonstrated. Of the 433 cases reported nationwide in 2002-2004 in whom vaccination status could be ascertained, 424 (97.9%) received no vaccine and none received 2 doses. Conclusion  This universal toddlers-only immunization program in Israel demonstrated not only high effectiveness of hepatitis A vaccination but also marked herd protection, challenging the need for catch-up hepatitis A vaccination programs.      

A population-based study of inflicted traumatic brain injury in young children

Context  Physical abuse is a leading cause of serious head injury and death in children aged 2 years or younger. The incidence of inflicted traumatic brain injury (TBI) in US children is unknown. Objective  To determine the incidence of serious or fatal inflicted TBI in a defined US population of approximately 230 000 children aged 2 years or younger. Design, Setting, and Subjects  All North Carolina children aged 2 years or younger who were admitted to a pediatric intensive care unit or who died with a TBI in 2000 and 2001 were identified prospectively. Injuries were considered inflicted if accompanied by a confession or a medical and social service agency determination of abuse. Main Outcome Measure  Incidence of inflicted TBI. Multivariate logistic regression models were used to compare children with inflicted injuries with those with noninflicted injuries and with the general state population aged 2 years or younger. Results  A total of 152 cases of serious or fatal TBI were identified, with 80 (53%) incurring inflicted TBI. The incidence of inflicted traumatic brain injury in the first 2 years of life was 17.0 (95% confidence interval [CI], 13.3-20.7) per 100 000 person-years. Infants had a higher incidence than children in the second year of life (29.7 [95% CI, 22.9-36.7] vs 3.8 [95% CI, 1.3-6.4] per 100 000 person-years). Boys had a higher incidence than girls (21.0 [95% CI, 15.1-26.6] vs 13.0 [95% CI, 8.4-17.7] per 100 000 person-years). Relative to the general population, children who incurred an increased risk of inflicted injury were born to young mothers (21 years), non–European American, or products of multiple births. Conclusions  In this population of North Carolina children, the incidence of inflicted TBI varied by characteristics of the injured children and their mothers. These data may be helpful for informing preventive interventions.      

Impact of varicella vaccination on health care utilization

Context  Since varicella vaccine was first recommended for routine immunization in the United States in 1995, the incidence of disease has dropped substantially. However, national surveillance data are incomplete, and comprehensive data regarding outpatient as well as hospital utilization have not been reported. Objective  To examine the impact of the varicella vaccination program on medical visits and associated expenditures. Design, Setting, and Patients  Retrospective population-based study examining the trends in varicella health care utilization, based on data from the MarketScan databases, which include enrollees (children and adults) of more than 100 health insurance plans of approximately 40 large US employers, from 1994 to 2002. Main Outcome Measures  Trends in rates of varicella-related hospitalizations and ambulatory visits and direct medical expenditures for hospitalizations and ambulatory visits, analyzed using 1994 and 1995 as the prevaccination baseline. Results  From the prevaccination period to 2002, hospitalizations due to varicella declined by 88% (from 2.3 to 0.3 per 100 000 population) and ambulatory visits declined by 59% (from 215 to 89 per 100 000 population). Hospitalizations and ambulatory visits declined in all age groups, with the greatest declines among infants younger than 1 year. Total estimated direct medical expenditures for varicella hospitalizations and ambulatory visits declined by 74%, from an average of $84.9 million in 1994 and 1995 to $22.1 million in 2002. Conclusion  Since the introduction of the varicella vaccination program, varicella hospitalizations, ambulatory visits, and their associated expenditures have declined dramatically among all age groups in the United States.      

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.      

Neurological and neuromuscular disease as a risk factor for respiratory failure in children hospitalized with influenza infection

Context  The Advisory Committee on Immunization Practices (ACIP) recommends annual influenza vaccination for children with certain chronic medical conditions to prevent serious complications of influenza infection. Little is known about the relative contribution of each of these chronic medical conditions to the development of serious influenza-associated complications. Objective  To identify chronic medical conditions that are associated with respiratory failure in children hospitalized with community-acquired laboratory-confirmed influenza. Design, Setting, and Patients  A retrospective cohort study of patients aged 21 years or younger hospitalized at The Children’s Hospital of Philadelphia with community-acquired laboratory-confirmed influenza during 4 consecutive influenza seasons (June 2000 through May 2004). We examined 9 ACIP-designated high-risk chronic medical conditions and 3 additional chronic medical conditions (neurological and neuromuscular disease [NNMD], gastroesophageal reflux disease [GERD], and history of prematurity) that in recent studies have been associated with influenza hospitalization and severe influenza-related complications. Main Outcome Measures  Rate and odds ratio (OR) of respiratory failure, defined as need for mechanical ventilation. Results  Of 745 children hospitalized with community-acquired laboratory-confirmed influenza, 322 (43%) had 1 or more ACIP-designated high-risk chronic medical conditions. Neurological and neuromuscular disease, GERD, and history of prematurity were present in 12%, 14%, and 3%, of children, respectively. Thirty-two children (4.3%) developed respiratory failure. In multivariate logistic regression analyses, conditions associated with respiratory failure included NNMD (OR, 6.0; 95% confidence interval [CI], 2.7-13.5), chronic pulmonary disease other than asthma (OR, 4.8; 95% CI, 1.5-15.1), and cardiac disease (OR, 4.0; 95% CI, 1.6-10.2). The predicted probabilities of respiratory failure derived from the multivariate model were 12% (95% CI, 7%-20%), 9% (95% CI, 3%-23%), and 8% (95% CI, 4%-18%) for children with NNMD, chronic pulmonary disease, and cardiac disease, respectively. Conclusions  These results support the ACIP’s recent decision to add NNMD to the list of conditions for which annual influenza vaccine is recommended in children. Neurologists and primary care pediatricians should be alerted to the increased risk of respiratory failure and the importance of influenza vaccination in children with NNMD.      

Cost-effectiveness Analysis of a Rotavirus Immunization Program for the United States

Context.— Rotavirus is the most common cause of severe diarrhea in children, and a live, oral vaccine may soon be licensed for prevention. Objective.— To estimate the economic impact of a national rotavirus immunization program in the United States. Design.— Cost-effectiveness was analyzed from the perspectives of the health care system and society. A decision tree used estimates of disease burden, costs, vaccine coverage, efficacy, and price obtained from published and unpublished sources. Intervention.— The proposed vaccine would be administered to infants at ages 2, 4, and 6 months as part of the routine schedule of childhood immunizations. Main Outcome Measures.— Total costs, outcomes prevented, and incremental cost-effectiveness. Results.— A routine, universal rotavirus immunization program would prevent 1.08 million cases of diarrhea, avoiding 34000 hospitalizations, 95000 emergency department visits, and 227000 physician visits in the first 5 years of life. At $20 per dose, the program would cost $289 million and realize a net loss of $107 million to the health care system—$103 per case prevented. The program would provide a net savings of $296 million to society. Threshold analysis identified a break-even price per dose of $9 for the health care system and $51 for the societal perspective. Greater disease burden and greater vaccine efficacy and lower vaccine price increased cost-effectiveness. Conclusions.— A US rotavirus immunization program would be cost-effective from the perspectives of society and the health care system, although the cost of the immunization program would not be fully offset by the reduction in health care cost of rotavirus diarrhea unless the price fell to $9 per dose.      

Gaps in vaccine financing for underinsured children in the United States

Context  The number of new vaccines recommended for children and adolescents has nearly doubled during the past 5 years, and the cost of fully vaccinating a child has increased dramatically in the past decade. Anecdotal reports from state policy makers and clinicians suggest that new gaps have arisen in financial coverage of vaccines for children who are underinsured (ie, have private insurance that does not cover all recommended vaccines). In 2000, approximately 14% of children were underinsured for vaccines in the United States. Objectives  To describe variation among states in the provision of new vaccines to underinsured children and to identify barriers to state purchase and distribution of new vaccines. Design, Setting, and Participants  A 2-phase mixed-methods study of state immunization program managers in the United States. The first phase included 1-hour qualitative telephone interviews conducted from November to December 2005 with 9 program managers chosen to represent different state vaccine financing policies. The second phase incorporated findings from phase 1 to develop a national telephone and paper-based survey of state immunization program managers that was conducted from January to June 2006. Main Outcome Measures  Percentage of states in which underinsured children are unable to receive publicly purchased vaccines in the private or public sectors. Results  Immunization program managers from 48 states (96%) participated in the study. Underinsured children were not eligible to receive publicly purchased meningococcal conjugate or pneumococcal conjugate vaccines in the private sector in 70% and 50% of states, respectively, or in the public sector in 40% and 17% of states, respectively. Due to limited financing for new vaccines, 10 states changed their policies for provision of publicly purchased vaccines between 2004 and early 2006 to restrict access to selected new vaccines for underinsured children. The most commonly cited barriers to implementation in underinsured children were lack of sufficient federal and state funding to purchase vaccines. Conclusions  The current vaccine financing system has resulted in gaps for underinsured children in the United States, many of whom are now unable to receive publicly purchased vaccines in either the private or public sectors. Additional strategies are needed to ensure financial coverage for all vaccines, particularly new vaccines, among this vulnerable population.      

Burden, features, and outcome of neurological involvement in acute falciparum malaria in Kenyan children

Context  Plasmodium falciparum appears to have a particular propensity to involve the brain but the burden, risk factors, and full extent of neurological involvement have not been systematically described. Objectives  To determine the incidence and describe the clinical phenotypes and outcomes of neurological involvement in African children with acute falciparum malaria. Design, Setting, and Patients  A review of records of all children younger than 14 years admitted to a Kenyan district hospital with malaria from January 1992 through December 2004. Neurological involvement was defined as convulsive seizures, agitation, prostration, or impaired consciousness or coma. Main Outcome Measures  The incidence, pattern, and outcome of neurological involvement. Results  Of 58 239 children admitted, 19 560 (33.6%) had malaria as the primary clinical diagnosis. Neurological involvement was observed in 9313 children (47.6%) and manifested as seizures (6563/17 517 [37.5%]), agitation (316/11 193 [2.8%]), prostration (3223/15 643 [20.6%]), and impaired consciousness or coma (2129/16 080 [13.2%]). In children younger than 5 years, the mean annual incidence of admissions with malaria was 2694 per 100 000 persons and the incidence of malaria with neurological involvement was 1156 per 100 000 persons. However, readmissions may have led to a 10% overestimate in incidence. Children with neurological involvement were older (median, 26 [interquartile range {IQR}, 15-41] vs 21 [IQR, 10-40] months; P<.001), had a shorter duration of illness (median, 2 [IQR, 1-3] vs 3 [IQR, 2-3] days; P<.001), and a higher geometric mean parasite density (42.0 [95% confidence interval {CI}, 40.0-44.1] vs 30.4 [95% CI, 29.0-31.8] x 10³/µL; P<.001). Factors independently associated with neurological involvement included past history of seizures (adjusted odds ratio [AOR], 3.50; 95% CI, 2.78-4.42), fever lasting 2 days or less (AOR, 2.02; 95% CI, 1.64-2.49), delayed capillary refill time (AOR, 3.66; 95% CI, 2.40-5.56), metabolic acidosis (AOR, 1.55; 95% CI, 1.29-1.87), and hypoglycemia (AOR, 2.11; 95% CI, 1.31-3.37). Mortality was higher in patients with neurological involvement (4.4% [95% CI, 4.2%-5.1%] vs 1.3% [95% CI, 1.1%-1.5%]; P<.001). At discharge, 159 (2.2%) of 7281 patients had neurological deficits. Conclusions  Neurological involvement is common in children in Kenya with acute falciparum malaria, and is associated with metabolic derangements, impaired perfusion, parasitemia, and increased mortality and neurological sequelae. This study suggests that falciparum malaria exposes many African children to brain insults.      

Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine

Context  A conjugate vaccine targeting 7 pneumococcal serotypes was licensed for young children in 2000. In contrast to the 23-valent polysaccharide vaccine used in adults, the 7-valent conjugate vaccine affects pneumococcal carriage and transmission. Early after its introduction, incidence of invasive pneumococcal disease declined among older adults, a group at high risk for pneumococcal disease. Objective  To determine among adults aged 50 years or older whether incidence of invasive pneumococcal disease, disease characteristics, or the spectrum of patients acquiring these illnesses have changed over the 4 years since pneumococcal conjugate vaccine licensure. Design, Setting, and Population  Population-based surveillance of invasive pneumococcal disease in 8 US geographic areas (total population, 18 813 000), 1998-2003. Main Outcome Measures  Incidence of invasive pneumococcal disease by pneumococcal serotype and other characteristics; frequency among case patients of comorbid conditions and other factors influencing mortality. Results  Incidence of invasive pneumococcal disease among adults aged 50 years or older declined 28% (95% confidence interval [CI], –31% to –24%), from 40.8 cases/100 000 in 1998-1999 to 29.4 in 2002-2003. Among those aged 65 years or older, the 2002-2003 rate (41.7 cases/100 000) was lower than the Healthy People 2010 goal (42 cases/100 000). Among adults aged 50 years or older, incidence of disease caused by the 7 conjugate vaccine serotypes declined 55% (95% CI, –58% to –51%) from 22.4 to 10.2 cases/100 000. In contrast, disease caused by any of the 16 serotypes only in polysaccharide vaccine did not change, and disease caused by serotypes not in either vaccine increased somewhat, from 6.0 to 6.8 cases/100 000 (13%; 95% CI, 1% to 27%). Between 1998-1999 and 2002-2003, the proportion of case-patients with human immunodeficiency virus infection increased from 1.7% (47/2737) to 5.6% (124/2231) (P<.001), and those with any comorbid condition that is an indication for pneumococcal polysaccharide vaccination increased from 62.3% (1842/2955) to 72.0% (1721/2390) (P<.001). Conclusions  Our findings indicate that use of conjugate vaccine in children has substantially benefited older adults. However, persons with certain comorbid conditions may benefit less than healthier persons from the indirect effects of the new vaccine.      

Association between thimerosal-containing vaccine and autism

Context  Mercuric compounds are nephrotoxic and neurotoxic at high doses. Thimerosal, a preservative used widely in vaccine formulations, contains ethylmercury. Thus it has been suggested that childhood vaccination with thimerosal-containing vaccine could be causally related to neurodevelopmental disorders such as autism. Objective  To determine whether vaccination with a thimerosal-containing vaccine is associated with development of autism. Design, Setting, and Participants  Population-based cohort study of all children born in Denmark from January 1, 1990, until December 31, 1996 (N = 467 450) comparing children vaccinated with a thimerosal-containing vaccine with children vaccinated with a thimerosal-free formulation of the same vaccine. Main Outcome Measures  Rate ratio (RR) for autism and other autistic-spectrum disorders, including trend with dose of ethylmercury. Results  During 2 986 654 person-years, we identified 440 autism cases and 787 cases of other autistic-spectrum disorders. The risk of autism and other autistic-spectrum disorders did not differ significantly between children vaccinated with thimerosal-containing vaccine and children vaccinated with thimerosal-free vaccine (RR, 0.85 [95% confidence interval {CI}, 0.60-1.20] for autism; RR, 1.12 [95% CI, 0.88-1.43] for other autistic-spectrum disorders). Furthermore, we found no evidence of a dose-response association (increase in RR per 25 µg of ethylmercury, 0.98 [95% CI, 0.90-1.06] for autism and 1.03 [95% CI, 0.98-1.09] for other autistic-spectrum disorders). Conclusion  The results do not support a causal relationship between childhood vaccination with thimerosal-containing vaccines and development of autistic-spectrum disorders.      

Risk of injury to child passengers in compact extended-cab pickup trucks

Context  An increasing number of compact pickup trucks can accommodate restrained rear occupants. Rear seats in these pickup trucks are exempt from regulatory safety testing though their relative safety has not been determined. Objectives  To evaluate the risk of injury to children in compact extended-cab pickup trucks compared with children in other vehicles and to determine if any unique hazards exist. Design  Cross-sectional study of children aged 15 years or younger in crashes of insured vehicles, with data collected via insurance claim records and a telephone survey. Setting and Participants  Probability sample of 7192 multirow vehicles involved in crashes, with 11 335 child occupants, in 3 large US regions from December 1, 1998, to November 30, 2000. Main Outcome Measure  Relative risk of injury, defined as concussions and more serious brain injuries, spinal cord injuries, internal organ injuries, extremity fractures, and facial lacerations, estimated by odds ratios (ORs) adjusting for age, restraint use, point of impact, vehicle weight, and crash severity. Results  Injuries were reported for 1356 children, representing 1.6% of the population. Children in compact extended-cab pickup trucks were at greater risk of injury than children in other vehicles (adjusted OR, 2.96; 95% confidence interval [CI], 1.68-5.21). Children in the rear seats of compact pickup trucks were at substantially greater risk of injury than rear-seated children in other vehicles (adjusted OR, 4.75; 95% CI, 2.39-9.43). Children seated in the front seat of compact extended-cab pickup trucks were at greater risk of injury than children in the front seats of other vehicles, but this risk was not statistically significant (adjusted OR, 1.70; 95% CI, 0.78-3.69). Conclusions  Children in compact extended-cab pickup trucks are not as safe as children in other vehicles, primarily due to the increased relative risk of injury in the back seat. For families with another choice of vehicle, clinicians should advise parents against transporting children in compact pickup trucks. The current exemption for regulatory testing for occupant protection in the rear seats of compact pickup trucks should be reconsidered.      

Follow-up testing among children with elevated screening blood lead levels

Context  Follow-up testing after an abnormal screening blood lead level is a key component of lead poisoning prevention. Objectives  To measure the proportion of children with elevated screening lead levels who have follow-up testing and to determine factors associated with such care. Design, Setting, and Participants  Retrospective, observational cohort study of 3682 Michigan Medicaid-enrolled children aged 6 years or younger who had a screening blood lead level of at least 10 µg/dL (0.48 µmol/L) between January 1, 2002, and June 30, 2003. Main Outcome Measure  Testing within 180 days of an elevated screening lead level. Results  Follow-up testing was received by 53.9% (95% confidence interval [CI], 52.2%-55.5%) of the children. In multivariate analysis adjusting for age, screening blood lead level results, and local health department catchment area, the relative risk of follow-up testing was lower for Hispanic or nonwhite children than for white children (0.91; 95% CI, 0.87-0.94), for children living in urban compared with rural areas (0.92; 95% CI, 0.89-0.96), and for children living in high- compared with low-risk lead areas (0.94; 95% CI, 0.92-0.96). Among children who did not have follow-up testing, 58.6% (95% CI, 56.3%-61.0%) had at least 1 medical encounter in the 6-month period after the elevated screening blood lead level, including encounters for evaluation and management (39.3%; 95% CI, 36.9%-41.6%) or preventive care (13.2%; 95% CI, 11.6%-14.8%). Conclusions  The rate of follow-up testing after an abnormal screening blood lead level was low, and children with increased likelihood of lead poisoning were less likely to receive follow-up testing. At least half of the children had a missed opportunity for follow-up testing. The observed disparities of care may increase the burden of cognitive impairment among at-risk children.      

Prevalence and trends in overweight among US children and adolescents, 1999-2000

Context  The prevalence of overweight among children in the United States increased between 1976-1980 and 1988-1994, but estimates for the current decade are unknown. Objective  To determine the prevalence of overweight in US children using the most recent national data with measured weights and heights and to examine trends in overweight prevalence. Design, Setting, and Participants  Survey of 4722 children from birth through 19 years of age with weight and height measurements obtained in 1999-2000 as part of the National Health and Nutrition Examination Survey (NHANES), a cross-sectional, stratified, multistage probability sample of the US population. Main Outcome Measure  Prevalence of overweight among US children by sex, age group, and race/ethnicity. Overweight among those aged 2 through 19 years was defined as at or above the 95th percentile of the sex-specific body mass index (BMI) for age growth charts. Results  The prevalence of overweight was 15.5% among 12- through 19-year-olds, 15.3% among 6- through 11-year-olds, and 10.4% among 2- through 5-year-olds, compared with 10.5%, 11.3%, and 7.2%, respectively, in 1988-1994 (NHANES III). The prevalence of overweight among non-Hispanic black and Mexican-American adolescents increased more than 10 percentage points between 1988-1994 and 1999-2000. Conclusion  The prevalence of overweight among children in the United States is continuing to increase, especially among Mexican-American and non-Hispanic black adolescents.      

Long-term efficacy of BCG vaccine in American Indians and Alaska Natives: A 60-year follow-up study

Context  The duration of protection from tuberculosis of BCG vaccines is not known. Objective  To determine the long-term duration of protection of a BCG vaccine that was previously found to be efficacious. Design  Retrospective record review using Indian Health Service records, tuberculosis registries, death certificates, and supplemental interviews with trial participants. Setting and Participants  Follow-up for the period 1948-1998 among American Indians and Alaska Natives who participated in a placebo-controlled BCG vaccine trial during 1935-1938 and who were still at risk of developing tuberculosis. Data from 1483 participants in the BCG vaccine group and 1309 in the placebo group were analyzed. Main Outcome Measures  Efficacy of BCG vaccine, calculated for each 10-year interval using a Cox regression model with time-dependent variables based on tuberculosis events occurring after December 31, 1947 (end of prospective case finding). Results  The overall incidence of tuberculosis was 66 and 138 cases per 100 000 person-years in the BCG vaccine and placebo groups, respectively, for an estimate of vaccine efficacy of 52% (95% confidence interval, 27%-69%). Adjustments for age at vaccination, tribe, subsequent BCG vaccination, chronic medical illness, isoniazid use, and bacille Calmette-Guérin strain did not substantially affect vaccine efficacy. There was slight but not statistically significant waning of the efficacy of BCG vaccination over time, greater among men than women. Conclusion  In this trial, BCG vaccine efficacy persisted for 50 to 60 years, suggesting that a single dose of an effective BCG vaccine can have a long duration of protection.      

Effect of intensive handwashing promotion on childhood diarrhea in high-risk communities in Pakistan: a randomized controlled trial

Context  Washing hands with soap prevents diarrhea, but children at the highest risk of death from diarrhea are younger than 1 year, too young to wash their own hands. Previous studies lacked sufficient power to assess the impact of household handwashing on diarrhea in infants. Objective  To evaluate the effect of promoting household handwashing with soap among children at the highest risk of death from diarrhea. Design, Setting, and Participants  A cluster randomized controlled trial of 36 low-income neighborhoods in urban squatter settlements in Karachi, Pakistan. Field workers visited participating households at least weekly from April 15, 2002, to April 5, 2003. Eligible households located in the study area had at least 2 children younger than 15 years, at least 1 of whom was younger than 5 years. Interventions  Weekly visits in 25 neighborhoods to promote handwashing with soap after defecation and before preparing food, eating, and feeding a child. Within intervention neighborhoods, 300 households (1523 children) received a regular supply of antibacterial soap and 300 households (1640 children) received plain soap. Eleven neighborhoods (306 households and 1528 children) comprised the control group. Main Outcome Measure  Incidence density of diarrhea among children, defined as the number of diarrheal episodes per 100 person-weeks of observation. Results  Children younger than 15 years living in households that received handwashing promotion and plain soap had a 53% lower incidence of diarrhea (95% confidence interval [CI], –65% to –41%) compared with children living in control neighborhoods. Infants living in households that received handwashing promotion and plain soap had 39% fewer days with diarrhea (95% CI, –61% to –16%) vs infants living in control neighborhoods. Severely malnourished children (weight for age z score, <–3.0) younger than 5 years living in households that received handwashing promotion and plain soap had 42% fewer days with diarrhea (95% CI, –69% to –16%) vs severely malnourished children in the control group. Similar reductions in diarrhea were observed among children living in households receiving antibacterial soap. Conclusion  In a setting in which diarrhea is a leading cause of child death, improvement in handwashing in the household reduced the incidence of diarrhea among children at high risk of death from diarrhea.      

Incidence of childhood distal forearm fractures over 30 years: a population-based study

Context  The incidence of distal forearm fractures in children peaks around the time of the pubertal growth spurt, possibly because physical activity increases at the time of a transient deficit in cortical bone mass due to the increased calcium demand during maximal skeletal growth. Changes in physical activity or diet may therefore influence risk of forearm fracture. Objective  To determine whether there has been a change in the incidence of distal forearm fractures in children in recent years. Design, Setting and Patients  Population-based study among Rochester, Minn, residents younger than 35 years with distal forearm fractures in 1969-1971, 1979-1981, 1989-1991, and 1999-2001. Main Outcome Measure  Estimated incidence of distal forearm fractures in 4 time periods. Results  Comparably age- and sex-adjusted annual incidence rates per 100 000 increased from 263.3 (95% confidence interval [CI], 231.1-295.4) in 1969-1971 to 322.3 (95% CI, 285.3-359.4) in 1979-1981 and to 399.8 (95% CI, 361.0-438.6) in 1989-1991 before leveling off at 372.9 (95% CI, 339.1-406.7) in 1999-2001. Age-adjusted incidence rates per 100 000 were 32% greater among male residents in 1999-2001 compared with 1969-1971 (409.4 [95% CI, 359.9-459.0] vs 309.4 [95% CI, 259.3-359.5]; P = .01) and 56% greater among female residents in the same time periods (334.3 [95% CI, 288.6-380.1] vs 214.6 [95% CI, 174.9-254.4]; P<.001). The peak incidence and greatest increase occurred between ages 11 and 14 years in boys and 8 and 11 years in girls. Conclusions  There has been a statistically significant increase in the incidence of distal forearm fractures in children and adolescents, but whether this is due to changing patterns of physical activity, decreased bone acquisition due to poor calcium intake, or both is unclear at present. Given the large number of childhood fractures, however, studies are needed to define the cause(s) of this increase.      

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.      

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.