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Fc gammaRIIa polymorphism in human immunodeficiency virus-infected children with invasive pneumococcal disease.

Invasive pneumococcal disease (IPD) occurs frequently in HIV-infected children and adults. Defects in complement function, opsonic capsular antibodies, and Fc receptor antibody-mediated phagocytosis could contribute to impaired host defense against Streptococcus pneumoniae. The objective of this study was to define the distribution of the three Fc gammaRIIa genotypes in HIV+ children, including those with IPD. Forty-eight HIV+ Hispanic children, including eight with IPD, followed at Bronx-Lebanon Hospital Center, Bronx, New York, nine HIV+ adults with IPD, and 56 HIV- Hispanic control subjects were studied. The children and adults were identified retrospectively except for one child who developed IPD during the study. Fc gammaRIIa genotypes were determined by PCR amplification of the Fc gammaRIIa locus from genomic DNA samples and hybridization of the PCR products with allele-specific oligonucleotides. Naturally occurring serum antibodies reactive with four pneumococcal polysaccharide serotypes were determined by ELISA in seven of eight children with IPD. There were no statistical differences in Fc gammaRIIa genotypes between HIV+ children with and without IPD, HIV+ adults with IPD, or HIV- Hispanics. The predominant IgG subclass of pneumococcal polysaccharide binding antibodies in the seven HIV+ children with IPD studied was IgG1. The distribution of Fc gammaRIIa genotypes in HIV+ children with and without IPD is similar to that of the normal Hispanic population. The prospect of passive immunotherapy with specific anticapsular antibodies might be a promising alternative for the treatment and/or prevention of IPD in HIV+ children and other immunodeficient groups.

AIDS-Related Opportunistic Infections↗

Postlicensure surveillance for pneumococcal invasive disease after use of heptavalent pneumococcal conjugate vaccine in Northern California Kaiser Permanente.

OBJECTIVE: To assess the direct and indirect effects of the introduction of routine use of pneumococcal conjugate vaccine in infants and toddlers at risk for invasive disease caused by vaccine serotypes and nonvaccine serotypes in vaccinated children and unvaccinated children of the same age. Secondary objectives included determination of the risk of pneumococcal infections in unvaccinated older children and adults in the same population and the impact of vaccine introduction on patterns of antimicrobial resistance. METHODS: Northern California Kaiser Permanente provides integrated comprehensive care to 3.1 million people and has an annual birth cohort of 38,000 infants. Microbiology services use a regional laboratory. Automated laboratory results, immunization records as well as diagnoses for inpatient and outpatient utilization are available from clinical data bases. Beginning in April 2000, the heptavalent pneumococcal conjugate (PNCV7) vaccine was introduced into routine use in the Northern California Kaiser Permanente population. Cases of invasive pneumococcal disease were identified from the automated hospital diagnosis as well as laboratory databases for all individuals, vaccinees and nonvaccinees, inpatient and outpatient. For the purpose of these analyses, pneumococcal invasive disease was defined as a positive culture from a normally sterile site. RESULTS: As of March 2003, 157,471 children had received 1 dose or more of PNCV7, but only 24% of those <2 years of age received all 4 doses as a result of shortages of vaccine. During the last year of observation, no cases of vaccine serotype disease were seen in children <1 year of age compared with an incidence ranging between 51.5 and 98.2 cases per 100,000 person-years (16-34 cases per year) in the years before vaccine introduction. Similar reductions were seen in children <5 years of age. There was no evidence of any concomitant increase in pneumococcal disease caused by nonvaccine serotypes. High level resistance of pneumococci to penicillin fell from a peak of 15% in 2000 to 5% in the first half of 2003. Similar trends were seen for other antibiotics. CONCLUSION: The PNCV7 vaccine is highly effective in reducing the burden of pneumococcal disease in children <5 years of age, and there is evidence of a herd effect as well as a decrease in the antibiotic resistant in strains causing disease. For invasive disease, there is no current evidence of serotype replacement.

Adolescent↗

[Clinical effectiveness of seven-valent pneumococcal conjugate vaccine (Prevenar) against invasive pneumococcal diseases: prospects for children in France].

A seven-valent pneumococcal polysaccharide-CRM197 carrier protein conjugate vaccine (PNC7V; Prevenar, Wyeth, Paris) targets the serotypes (belonging to serogroups 14, 6, 19, 18, 23, 9, and 4) most often responsible for invasive pneumococcal disease (IPD) among children. A randomized, controlled, double-masked study among 37,868 children in northern California (Northern California Kaiser Permanente, USA) provided a per protocol vaccine efficacy value of 97.7% against invasive pediatric IPD due to the vaccine serotypes. The PNC7V vaccine was registered by the European Agency for the Evaluation of Medicinal Products (EMEA) in October 2000; a favorable "Community Marketing Decision" under the Centralized Procedure was granted in February 2001. PNC7V was recommended for most infants by the Conseil Supérieur d'Hygiène Publique de France in March 2002, on the advice of the Comité Technique des Vaccinations, as S. pneumoniae in children less than 2 years of age is the primary cause of bacterial meningitis and of mortality associated with community-acquired bacterial infections. The theoretical coverage of the vaccine towards pneumococcal invasive disease in France is about 80%, which represents one of the best serotype coverage estimates in Europe, and vaccines serotypes account for 90% of penicillin-nonsusceptible strains. Distinctive characteristics in France in terms of epidemiology, life style, and therapeutic attitudes justify a precise follow up of the consequences of the vaccination on a national level during the coming years. Hence, surveillance programs have been established: (i) to ascertain the future impact of large-scale PNC7V vaccination on invasive pneumococcal disease incidence, (ii) to follow the evolution of carriage and ecology of the pneumococcus, and (iii) to establish an active "vaccinovigilance".

Female↗

Population-based surveillance for childhood invasive pneumococcal disease in the era of conjugate vaccine.

BACKGROUND: Heptavalent pneumococcal conjugate vaccine was licensed in the United States in February 2000 and, following national guidelines, universally distributed in Massachusetts starting in July 2000 to children younger than 2 years of age and selected children 2-5 years of age. We performed statewide surveillance for all cases of invasive pneumococcal disease (IPD) in children younger than 18 years of age to determine risk features and contribution of vaccine failure to ongoing pneumococcal invasive disease. METHODS: Massachusetts pediatric IPD cases were identified via enhanced passive surveillance of microbiology laboratory reports of pneumococcal isolates from sterile body sites of children younger than 18 years for 2 years starting in October 2001. Serotyping was performed on isolates of Streptococcus pneumoniae from normally sterile body fluid. Case demographic and clinical data (including dates of prior doses of PCV7) were collected via follow-up telephone interviews with case primary care providers and/or parents. RESULTS: Between October 1, 2001 and September 30, 2003, 191 cases of IPD were identified statewide (138 in children younger than 5 years). Annual incidence rate for IPD was 17.4 per 100,000 children younger than 5 years, representing a decline of 69% when compared with annual incidence rate of 56.9 per 100,000 from Massachusetts statewide active surveillance performed 1990-1991. In 2001-2003, 30% of cases occurred in the first year of life (36.5 per 100,000), representing a 7.8-fold increased risk compared with children older than 1 year of age. Race-specific annual incidence rates in blacks and Hispanics were 2.3-fold (95% confidence interval, 1.21-4.42) and 1.9-fold (95% confidence interval, 1.06-3.37), greater than in whites. Fifty-nine cases were reported to have underlying comorbid conditions. Serotyping was available for 136 of 191 (71%) cases younger than 18 years; of isolates available for serotyping, 40 (29%) were vaccine serotype (ST), 31 (23%) vaccine-related ST and 65 (48%) nonvaccine ST. Seven of 40 cases with IPD caused by vaccine ST received at least 3 doses of PCV7 vaccine before IPD. CONCLUSIONS: Universal administration of PCV7 to children younger than 2 years of age and selective administration to children 2-5 years of age has resulted in a significant decline in IPD in Massachusetts. Children younger than 1 year of age, African American and Hispanic children and those with recognized comorbid illnesses (malignancy, human immunodeficiency virus, immune deficiency, nephrotic syndrome, etc.) continue to remain at risk for IPD. These risk features should be considered when evaluating febrile infants and children.

Adolescent↗

Invasive pneumococcal disease in central Australia.

Invasive pneumococcal disease remains a major problem in certain groups of people. We undertook a hospital-based review of all cases of invasive pneumococcal disease in central Australia over a 2-year period. We observed 79 cases of invasive disease in 78 patients. The incidence of invasive pneumococcal disease was highest in Aborigines under 5 years of age (1,025 cases per 100,000 population per year). The relative risk for Aborigines compared with non-Aborigines was 31.6 (95% CI, 12.8-78.1). Pneumonia was the commonest disease observed (82% of patients). Eight patients died (10.1%), and all of these patients had identifiable risk factors for pneumococcal disease. Serotyping showed that all except two isolates were covered by the existing 23-valent pneumococcal vaccine. These data reveal that Aborigines in central Australia have the highest reported rate of invasive pneumococcal disease in the world. A vaccination program in central Australia should decrease admissions and deaths due to pneumococcal disease.

Adolescent↗

Asthma as a risk factor for invasive pneumococcal disease.

BACKGROUND: The risk of invasive pneumococcal disease among persons with asthma is unknown. METHODS: We conducted a nested case-control study to examine the association between asthma and invasive pneumococcal disease. The study population included persons 2 to 49 years of age who were enrolled in Tennessee's Medicaid program (TennCare) for more than one year during the study period (1995 through 2002) and who resided in counties participating in a prospective laboratory-based program of surveillance for invasive pneumococcal disease. For each subject with invasive pneumococcal disease, 10 age-matched controls without invasive pneumococcal disease were randomly selected from the same population. TennCare files were queried to identify the presence of coexisting conditions that confer a high risk of pneumococcal disease. For the purpose of our study, asthma was defined by documentation of one or more inpatient or emergency-department diagnoses of asthma, two outpatient diagnoses, or the use of asthma-related medications. High-risk asthma was defined as asthma requiring admission to a hospital or a visit to an emergency department, the use of rescue therapy or long-term use of oral corticosteroids, or the dispensing of three or more prescriptions for beta-agonists within the year before enrollment in the study. RESULTS: A total of 635 persons with invasive pneumococcal disease and 6350 controls were identified, of whom 114 (18.0 percent) and 516 (8.1 percent), respectively, had asthma. Persons with asthma had an increased risk of invasive pneumococcal disease (adjusted odds ratio, 2.4; 95 percent confidence interval, 1.9 to 3.1) as compared with controls. Among those without coexisting conditions, the annual incidence of invasive pneumococcal disease was 4.2 episodes per 10,000 persons with high-risk asthma and 2.3 episodes per 10,000 persons with low-risk asthma, as compared with 1.2 episodes per 10,000 persons without asthma. CONCLUSIONS: Asthma is an independent risk factor for invasive pneumococcal disease. The risk among persons with asthma was at least double that among controls.

Adolescent↗

Effectiveness of the 23-valent polysaccharide vaccine against invasive pneumococcal disease in Navajo adults.

Invasive pneumococcal disease occurs 2-3-fold more often among Navajo adults than among adults in the general United States population. The objective of this observational study was to determine the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) among Navajo adults. Active surveillance identified cases of invasive pneumococcal disease during 1996-1997. Three control patients per case patient were matched according to underlying medical conditions, sex, age, and location of medical care. Effectiveness was calculated by regression analysis of case-control sets and by indirect cohort methodology. Diabetes and alcoholism occurred in 41% and 43% of 108 case patients, respectively; 62% of case patients and 64% of control patients were immunized. Overall vaccine effectiveness was 26% (95% confidence interval [CI], -29% to 58%); 15% (95% CI, -116% to 67%) for patients with diabetes and -5% (95% CI, -141% to 54%) for patients with alcoholism. Overall vaccine effectiveness, as determined by use of the indirect cohort methodology, was 35% (95% CI, -33% to 69%). PPV23 was not significantly effective among Navajo adults and may be inadequate to prevent serious pneumococcal disease in this population.

Adult↗

Recurrent invasive pneumococcal disease in individuals with human immunodeficiency virus infection.

The proportion of relapses and reinfections that are potentially preventable by vaccine in human immunodeficiency virus (HIV)-infected persons with recurrent pneumococcal disease is unknown. Isolates from HIV-infected individuals from Baltimore with recurrent pneumococcal invasive disease were collected from 1 January 1995 through 31 December 2000. Serotyping and pulsed-field gel electrophoresis were performed. From 1 January 1995 through 31 December 1998, 14.9% (404/2717) of those who had a pneumococcal infection were HIV infected. The recurrence rate among HIV-infected individuals was 6.4-fold higher than that among individuals without HIV infection (P<.01). Among recurrent infections in 41 individuals, there were 42 reinfections and 6 relapses. All relapses and 91% (70/77) of reinfections were due to serotypes covered by the 23-valent pneumococcal polysaccharide vaccine. Reinfection was more common than relapse among HIV-infected individuals with recurrent pneumococcal disease. Although a substantial proportion of recurrent pneumococcal infections was potentially preventable by vaccine, creating an effective vaccine may be challenging for this population.

Adult↗

The Georgia Emerging Infections Program: monitoring trends in invasive pneumococcal disease.

The active, population-based surveillance system of the Georgia EIP has provided valuable insights into the characteristics of invasive pneumococcal disease in Georgia and continues to provide an important mechanism to assess the impact of the newly introduced PCV7 vaccine. The problem of antimicrobial resistance has been carefully documented among isolates from invasive pneumococcal disease in all age groups, particularly young children. Fluoroquinolone resistance is now present in our area and will require close monitoring in the coming months and years. Over 80% of invasive pneumococcal disease and over 85% of penicillin and cefotaxime resistant invasive disease occurring in young children in our surveillance area involve serotypes included in the new conjugate vaccine approved for use in children. Preliminary data suggest an early decline in invasive pneumococcal disease in young children has occurred since the introduction of the conjugate vaccine and the effect upon the prevalence of antimicrobial resistance remains to be determined. The high rates of invasive pneumococcal disease, the significant associated morbidity and mortality and antimicrobial resistance highlight the need for enhanced prevention measures in both adults and children. Ongoing surveillance in the Georgia EIP will allow accurate measurement of the impact of prevention efforts, provide essential information on trends in antimicrobial resistance and document any changes in the pneumococcal serotypes responsible for invasive disease in the conjugate vaccine era.

Adolescent↗

[Risk factors of mortality in invasive pneumococcal disease].

BACKGROUND AND OBJECTIVE: To analyze the risk factors associated with mortality in invasive pneumococcal disease in the university hospital Fundación Jiménez Díaz (Madrid, Spain) during 11 years. PATIENTS AND METHOD: We performed a retrospective study of patients attending the emergency service of the hospital from January 1993 to August 2003. We registered data on mortality, clinical and microbiological evolution and relapses. RESULTS: We studied 263 patients with pneumococcal baceteremia and invasive disease caused by Streptococcus pneumoniae (pneumonia, meningitis, sepsis, bacteremia of unknown origin and oligoarthritis). Mortality was 12.5%. Variables associated with mortality in a logistic regression analysis included absence of leukocytosis (p = 0.04), acidosis (p < 0.01), respiratory signs and symptoms (tachypnea, pleuritic pain) (p = 0.02), and neurologic manifestations (decreased consciousness level; (p < 0.01). CONCLUSION: Patients at highest risk of death because of invasive pneumococcal disease are critically ill, with no leukocytosis, with severe respiratory or neurological symptoms and undergoing invasive procedures such as mechanical ventilation and tracheostomy.

Female↗

Childhood invasive pneumococcal disease in Tasmania, 1994-2000.

OBJECTIVE: To describe the burden of invasive pneumococcal disease in Tasmanian children, including age-specific incidence and antibiotic-resistance pattern. METHODS: A population-based retrospective study was carried out, examining cases of childhood disease associated with isolates of Streptococcus pneumoniae from normally sterile sites, identified via scrutiny of laboratory records at all major Tasmanian laboratories during a 7-year period between January 1994 and December 2000. Medical records were sub-sequently examined for information describing the clinical syndrome and course of disease. RESULTS: Invasive pneumococcal disease was identified in 76 children during the 7-year period. The incidence per 100 000 children was 28.5 (95% CI 22.0-36.3) in children under 5 years and 54.3 (95% CI 40.2-71.8) in children under 2 years. The incidence of meningitis in children younger than 2 years was 12.2 (95% CI 6.1-21.8). Penicillin resistance was observed in 2.6% of cases, with no high level resistance. Predisposing conditions were identified in 34% of children with invasive disease. CONCLUSIONS: The incidence of invasive pneumococcal disease was comparable to many urban populations in Australia. The high rate of predisposing conditions supports the recommendations of the Australian Technical Advisory Group on Immunisation for targeted immunization in this group. The paucity of data describing Indigenous status is an argument for improved data collection in this area. The low level of penicillin resistance necessitates ongoing surveillance, and the lack of serotype information requires prospective data collection.

Adolescent↗

The epidemiology of invasive pneumococcal disease in children in Far North Queensland.

OBJECTIVES: To describe the epidemiology of invasive pneumococcal disease in children under 5 years of age in Far North Queensland and to examine the potential impact of a seven- and 11-valent conjugate pneumococcal vaccine. METHODS: A review of all cases of invasive pneumococcal disease in children under 5 years of age in Far North Queensland over a 9 year period (1992-2000). The distribution of the serotypes of isolates causing invasive pneumococcal disease was compared with the serotypes contained in the two vaccines. RESULTS: The annual incidence in indigenous and non-indigenous children under 5 years of age was 163 (95% confidence interval (CI) 122-213) and 42 (95% CI 31-55) cases per 100 000 children, respectively. For children under 2 years of age, these figures were 297 (95% CI 208-411) and 71 (95% CI 49-100), respectively. There was a greater variety of serotypes isolated from indigenous children (n=17) than from non-indigenous children (n=9; P < 0.01). The serotypes within the seven-valent vaccine accounted for 62% (95% CI 46-75%) and 88% (95% CI 76-95%) of the isolates from indigenous and non-indigenous children, respectively (P < 0.01). Serotypes within the 11-valent vaccine accounted for 72% (95% CI 57-84%) of the isolates from indigenous children under 5 years of age, but did not account for any extra isolates from non-indigenous children. CONCLUSION: Although the seven- and 11-valent conjugate pneumococcal vaccines cover only approximately 60 and 70%, respectively, of the isolates that cause invasive disease in indigenous children in Far North Queensland, they nevertheless have the potential to prevent much morbidity in and hospitalization of these children. It will be essential to maintain surveillance following the introduction of conjugate pneumococcal vaccines so as to monitor changes in the incidence of invasive pneumococcal disease, particularly in high-risk children.

Age Distribution↗

Has the seven-valent pneumococcal conjugate vaccine had an impact on invasive pneumococcal disease in Western Australia?

Enhanced surveillance for invasive pneumococcal disease (IPD) has been ongoing in Western Australia since 1996. We describe the epidemiology of invasive pneumococcal disease in children aged <2 years between 1996 and 2005. Pneumococcal conjugate vaccine has been offered to Aboriginal children and other high-risk children since July 2001 and to all Australian children since January 2005. A total of 1655 IPD cases were reported of whom 361 (55 Aboriginal) were aged <2 years. From 1996-2001 to 2002-2005, IPD incidence declined from 192 to 124/100,000/annum in Aboriginal children and from 70 to 56/100,000/annum in non-Aboriginal children. Incidence of IPD due to vaccine serotypes (VT) declined from 118 to 43/100,000/annum (p=0.05) in Aboriginal children and from 59 to 45/100,000/annum in non-Aboriginal children (p<0.001), with no increased incidence of disease due to non-vaccine serotypes. Continued surveillance is essential to measure the impact of the childhood pneumococcal conjugate vaccination program on IPD incidence and to identify the emergence of disease due to non-vaccine serotypes.

Adolescent↗

Seasonality of invasive pneumococcal disease: temporal relation to documented influenza and respiratory syncytial viral circulation.

BACKGROUND: Seasonal fluctuation in the incidence of invasive pneumococcal disease has been attributed to winter virus exposure (e.g., influenza and respiratory syncytial virus [RSV]). Evidence of a direct correlation of invasive pneumococcal disease with laboratory-confirmed virus seasons, however, is limited. Using two prospective surveillance networks, the temporal relation between invasive pneumococcal disease and isolation of circulating winter viruses was explored. METHODS: Episodes of invasive pneumococcal disease in five Tennessee counties were collected prospectively from January 1995 through June 2002. Virus seasons were defined using prospective laboratory-based surveillance. Correlation between weekly identification of invasive pneumococcal disease and laboratory isolation of RSV and influenza, as well as comparisons of the frequencies of invasive pneumococcal disease episodes during viral and nonviral seasons were determined. RESULTS: A total of 4147 invasive pneumococcal disease episodes were identified. Weekly frequency of invasive pneumococcal disease correlated directly with the weekly frequency of isolation of RSV (r = 0.56, P <0.001) and influenza (r= 0.40, P <0.001). The average weekly frequency of invasive pneumococcal disease during RSV and influenza seasons was higher than during the nonviral seasons (P <0.001 for each year). CONCLUSION: Weekly episodes of invasive pneumococcal disease correlated temporally with laboratory-confirmed weekly isolation of RSV and influenza, and the incidence of invasive pneumococcal disease was increased when these viruses were circulating in the community.

Adolescent↗

Changes in invasive Pneumococcal disease among HIV-infected adults living in the era of childhood pneumococcal immunization.

BACKGROUND: Adults infected with HIV have high rates of invasive pneumococcal disease. Introduction of pneumococcal conjugate vaccine for children could affect disease among HIV-infected adults. OBJECTIVE: To compare invasive pneumococcal disease among HIV-infected adults before and after the introduction of a pediatric conjugate vaccine. DESIGN: Active laboratory-based surveillance in an adult population of 10.8 million, including 38,314 living with AIDS. SETTING: 7 Active Bacterial Core surveillance areas in the United States. PATIENTS: All surveillance-area residents 18 to 64 years of age with Streptococcus pneumoniae isolated from a sterile site between 1998 and 2003. MEASUREMENTS: Ratio of the number of cases of invasive pneumococcal disease among HIV-infected adults to the estimated number of adults 18 to 64 years of age living with AIDS; serotype-specific subset analyses; and comparison of periods before and after introduction of conjugate vaccine by using exact tests. RESULTS: Of 8582 cases of invasive pneumococcal disease in adults, 2013 (24%) occurred among persons infected with HIV. Between baseline (1998 to 1999) and 2003, the ratio of invasive pneumococcal disease in HIV-infected adults to the number of adults living with AIDS in the surveillance areas decreased from 1127 to 919 cases per 100 000 AIDS population, a reduction of 19% (P = 0.002). Among HIV-infected adults, the ratio for disease caused by pneumococcal serotypes included in the conjugate vaccine decreased 62% (P < 0.001), although the ratio for disease caused by nonvaccine serotypes increased 44% (P < 0.001). LIMITATIONS: Ratios are proxy measures of incidence rates. The denominator of surveillance-area residents living with HIV infection was not available. CONCLUSIONS: Introduction of the pediatric conjugate vaccine was associated with an overall decrease in invasive pneumococcal disease among HIV-infected adults, despite increased disease caused by nonvaccine serotypes.

AIDS-Related Opportunistic Infections↗

Invasive pneumococcal disease in England and Wales: what is the true burden and what is the potential for prevention using 7 valent pneumococcal conjugate vaccine?

BACKGROUND: The annual reported incidence rates for laboratory confirmed invasive pneumococcal disease (IPD) underestimate the true burden of invasive disease attributable to pneumococcal infection. AIMS: To estimate the proportion of "unspecified" mortality of infectious cause in infants and young children aged 1 month to 4 years reported by the Office for National Statistics (ONS) in England and Wales that could reasonably be attributed to IPD, thereby revising the total number of deaths per year potentially attributable to IPD, and producing a more accurate figure for the number of deaths that may be prevented by a programme of pneumococcal conjugate vaccination. METHODS: Polymerase chain reaction, latex agglutination, and other alternate methodologies to microbiological culture have been applied in various studies to the detection of Streptococcus pneumoniae. Some of these tests have been shown to be more sensitive indicators of pneumococcal infection. In our analysis the implications of these tests were applied theoretically to the "unspecified" clinical deaths caused by septicaemia, meningitis, and pneumonia reported by the ONS, with a 20% correction/reduction factor for nasopharyngeal carriage which these sensitive tests may coincidentally detect. RESULTS: The ONS reported an average of 13 deaths per year (1989-99) in infants and children aged 1 month to 4 years caused by pneumococcal septicaemia, meningitis, or pneumonia. By applying the rates for the more sensitive tests to the most recent ONS "unspecified" mortality data available (1999), the actual annual number of deaths caused by IPD in the age group 1 month to 4 years is shown to be at least as high as 43. CONCLUSIONS: The mortality as a result of IPD in infants and young children may be at least three times the reported rate. The 7 valent pneumococcal conjugate vaccine may have the potential to prevent up to 26 (61%) of the IPD deaths per year in infants and young children in England and Wales alone.

Child, Preschool↗

Risk factors for primary invasive pneumococcal disease among children in Finland.

OBJECTIVE: To study risk factors for invasive pneumococcal disease among children. DESIGN: A population-based, case-control study of 149 cases and 284 controls matched for age, sex, and place of residence. SETTING: Finland, November 1986 through November 1989. PATIENTS AND CONTROLS: Patients were identified from a prospective nationwide surveillance for invasive bacterial diseases among children (0 to 15 years of age) through a network of bacteriologic laboratories. Two matched controls were selected for 135 of the cases and one matched control for 14 of the cases from the respective cases' child health center or school. Questionnaires evaluating potential risk factors were mailed to families of cases and controls. RESULTS: An increased risk for invasive pneumococcal disease among children younger than 2 years was associated with day care center attendance (odds ratio [OR] = 36; 95% confidence interval [CI], 5.7 to 233), family day care (OR = 4.4; 95% CI, 1.7 to 12), and history of frequent otitis media (OR = 8.8; 95% CI, 2.5 31). For those at least 2 years of age, existence of siblings younger than school-age indicated increased risk for invasive pneumococcal disease (OR = 2.2; 95% CI, 1.1 to 4.4). CONCLUSIONS: Day care center attendance is a major risk factor for invasive pneumococcal disease for children younger than 2 years, with significantly higher risk than the risk associated with family day care.

Adolescent↗

Invasive pneumococcal disease in older adults residing in long-term care facilities and in the community.

OBJECTIVES: To examine the epidemiology of invasive pneumococcal disease in older adults hospitalized for invasive pneumococcal disease who are living in the community and in long-term care facilities (LTCFs) in the United States. DESIGN: Analysis of 2402 cases of invasive pneumococcal disease requiring hospitalization in 2000 and 2001 that the Centers for Disease Control and Prevention's Active Bacterial Core Surveillance collected in nine states. SETTING: Hospital. PARTICIPANTS: Hospitalized LTCF residents and community-living older adults in the United States. MEASUREMENTS: Age- and residence-specific pneumococcal disease incidence rates per 100000 persons, case-fatality rates, and trends in antimicrobial resistance. RESULTS: Nationally, the rate of invasive pneumococcal disease in LTCF residents was 194.2 cases per 100000 persons aged 65 and older and 44.6 for community-living older adults (relative risk=4.4, 95% confidence interval (CI)=4.2-4.5). Compared with community-living older adults, case-fatality rates were 1.9 times higher (30.8% vs 16.0%, 95% CI=1.5-2.5). Pneumococcal strains from LTCF residents were significantly more likely to be nonsusceptible to levofloxacin than strains from community- living older adults (5.7% vs 0.4%, P<.001). CONCLUSION: Older adults living in LTCFs are at a higher risk for invasive pneumococcal disease and death than are community-living older adults. Additionally, fluoroquinolone resistance is significantly higher in older adults living in LTCFs and may provide clues to emerging antimicrobial resistance in the general population.

Aged↗