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Pneumococcal vaccines: history, current status, and future directions.

Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and bacterial meningitis. Although effective antimicrobial drugs have reduced case fatality, the pneumococcus remains a leading global cause of morbidity and mortality. Therefore, prevention of infection by vaccination with the pneumococcal polysaccharide vaccine is recommended for persons at high risk for serious pneumococcal disease, such as the elderly and individuals with certain underlying medical conditions. Pneumococcal polysaccharide vaccines are safe and effective for the prevention of invasive infection among immunocompetent children and adults but are not immunogenic in infants. Conjugation of pneumococcal polysaccharides to a carrier protein improves immune responses among infants, and conjugate vaccines are currently being evaluated in large efficacy trials. The role of pneumococcal conjugate vaccines in adults has not been determined. Pneumococcal vaccines directed against pneumococcal proteins and DNA vaccines that induce anti-pneumococcal antibodies have been evaluated in animal models and may someday provide complementary or alternative methods for preventing pneumococcal infection. Improved utilization of the pneumococcal polysaccharide vaccine and continued development of improved vaccines are essential, and the emergence of drug-resistant strains of S. pneumoniae highlights the importance of preventing pneumococcal infections by vaccination.

Aged↗

Is the recommendation for pneumococcal vaccination of HIV patients evidence based?

BACKGROUND: both the current NHMRC guidelines of Australia and the USPHS/IDSA guidelines recommend pneumococcal vaccine be given to all patients with HIV infection despite a paucity of data to support these recommendations. OBJECTIVES: the aim of this study was to assess the incidence of invasive pneumococcal disease and use of pneumococcal vaccine in HIV-infected patients at The Alfred Hospital, Melbourne, Australia, and to review the evidence for the current recommendations. STUDY DESIGN: a case record review of all HIV-infected patients followed at The Alfred Hospital diagnosed with pneumonia between 1 June 1996 and 1 June 2000 was performed. Main outcome measures were the incidence of invasive pneumococcal disease and the proportion of these individuals who received pneumococcal vaccination. RESULTS: Invasive pneumococcal disease was a relatively infrequent event with an incidence of 1.9 per 1000 person years. This rate is lower than the 8.2 per 1000 person years reported for confirmed disease by CDC. Of the 34 patients with either definite invasive, presumptive or possible pneumococcal disease, 16 (47%) had received pneumococcal vaccine, seven of these within 5 years prior to the episode of pneumonia. In 15 cases, the vaccine was administered when the CD4 cell count was <500 per microl. CONCLUSION: lack of efficacy data, rarity of invasive disease plus evidence of infrequent administration delivered predominantly to those who are least likely to benefit, has prompted us to question the value of routinely vaccinating all our HIV-infected patients with pneumococcal vaccine. Review of the published literature provides conflicting data in support of the current recommendations for administration of pneumococcal vaccine in HIV patients. It may be more cost-effective to concentrate efforts on strategies to improve adherence to ARV therapy, as this has unequivocally been shown to be associated with a reduction in the incidence of pneumococcal disease.

AIDS-Related Opportunistic Infections↗

Improving pneumococcal vaccination coverage among older people in Victoria.

Although pneumococcal vaccine is recommended by the National Health and Medical Research Council and is cost-effective in preventing invasive pneumococcal disease, it is the only vaccine on the standard schedule that is not nationally funded through public health grants to the States. In Victoria, the Department of Human Services has provided free pneumococcal vaccine to people aged 65 years and over since 1998. Pneumococcal vaccination was given in conjunction with the annual influenza vaccination program; 28.5% of the eligible cohort (95% CI, 24.8%-32.1%) received pneumococcal vaccine in 1998, giving an estimated cumulative coverage of 42% (13.4% had received it in 1997). We expect coverage will continue to increase over time, but revaccination every five years will present a substantial financial burden; access to vaccine is critical to improving coverage. Our experience in Victoria suggests that a nationally funded program, administered similarly to the influenza vaccination program, would dramatically increase pneumococcal vaccination coverage at a national level.

Adolescent↗

Factors predictive of increased influenza and pneumococcal vaccination coverage in long-term care facilities: the CMS-CDC standing orders program Project.

BACKGROUND: Between 1999 and 2002, a multistate demonstration project was conducted in long-term care facilities (LTCFs) to encourage implementation of standing orders programs (SOP) as evidence-based vaccine delivery strategies to increase influenza and pneumococcal vaccination coverage in LTCFs. OBJECTIVE: Examine predictors of increase in influenza and pneumococcal vaccination coverage in LTCFs. DESIGN: Intervention study. Self-administered surveys of LTCFs merged with data from OSCAR (On-line Survey Certification and Reporting System) and immunization coverage was abstracted from residents' medical charts in LTCFs. SETTING AND PARTICIPANTS: Twenty LTCFs were sampled from 9 intervention and 5 control states in the 2000 to 2001 influenza season for baseline and during the 2001 to 2002 influenza season for postintervention. INTERVENTION: Each state's quality improvement organization (QIO) promoted the use of standing orders for immunizations as well as other strategies to increase immunization coverage among LTCF residents. MAIN OUTCOME MEASURES: Multivariate analysis included Poisson regression to determine independent predictors of at least a 10 percentage-point increase in facility influenza and pneumococcal vaccination coverage. RESULTS: Forty-two (20%) and 59 (28%) of the facilities had at least a 10 percentage-point increase in influenza and pneumococcal immunizations, respectively. In the multivariate analysis, predictors associated with increase in influenza vaccination coverage included adoption of requirement in written immunization protocol to document refusals, less-demanding consent requirements, lower baseline influenza coverage, and small facility size. Factors associated with increase in pneumococcal vaccination coverage included adoption of recording pneumococcal immunizations in a consistent place, affiliation with a multifacility chain, and provision of resource materials. CONCLUSIONS: To improve the health of LTCF residents, strategies should be considered that increase immunization coverage, including written protocol for immunizations and documentation of refusals, documenting vaccination status in a consistent place in medical records, and minimal consent requirements for vaccinations.

Age Factors↗

Improving pneumococcal vaccination rates in an elderly population by patient education in an outpatient clinic.

BACKGROUND: Invasive pneumococcal disease is a major cause of morbidity and mortality in elderly patients. This study investigated the impact of a patient education intervention on the pneumococcal vaccination rate in elders. METHODS: Charts of all patients aged 65 years or older who visited a university ambulatory care clinic during a 3-month period were reviewed for pneumococcal vaccination status before the patients' arrival for an office visit. Those who did not have the vaccination were provided patient education in the waiting room. Data were collected on age, sex, race, and immunization status. The reasons for refusing the vaccination before or during this intervention also were obtained. The charts of patients who consented were flagged for the attending physician to order the vaccination if appropriate. RESULTS: Charts of 535 patients were reviewed for pneumococcal vaccination status. Of these patients, 291 had had a pneumococcal vaccination before the study. The cumulative vaccination rate increased significantly from 54 percent to 79 percent after the study intervention. The rate of pneumococcal vaccination was significantly lower among African-Americans than whites both before and after the patient education intervention. CONCLUSION: This study reports a substantial impact of patient education on improving pneumococcal vaccination rates in an elderly population. Most elders accept vaccination, and it can be delivered effectively without an additional visit.

Black or African American↗

Pneumococcal vaccination. Controversies and opportunities.

The morbidity and mortality associated with pneumococcal infections are preventable in many high-risk individuals by immunization with 23-valent pneumococcal vaccine. While the clinical effectiveness of the current vaccine is less than ideal, use of the vaccine is cost effective. In spite of recommendations for pneumococcal vaccination of elderly and other high-risk persons, and federal reimbursement for vaccination Medicare enrollees, it was estimated in 1985 that only 10% to 15% of this target population was immunized. Strategies for immunizing high-risk individuals with pneumococcal vaccine need to involve physicians, public health professionals, health advocacy groups, and persons in the targeted populations.

Antibodies, Bacterial↗

The health and economic benefits associated with pneumococcal vaccination of elderly persons with chronic lung disease.

BACKGROUND: More than 50% of the elderly population has not received pneumococcal vaccination. Uncertainty regarding the benefits of immunization, particularly for noninvasive disease, may contribute to the underuse of pneumococcal vaccine. OBJECTIVE: To assess the health and economic benefits associated with pneumococcal vaccination. METHODS: We conducted a 2-year retrospective cohort study among all elderly members of a staff-model managed care organization who had a baseline diagnosis of chronic lung disease. The study outcomes were assessed over 2 years, from November 15, 1993, through November 14, 1995, and included hospitalizations for pneumonia and influenza, death, and hospitalization costs. Using administrative data, we compared these outcomes for vaccinated and unvaccinated subjects using multivariate models to control for subjects' baseline demographic and health characteristics. The additive benefits of combined influenza and pneumococcal vaccination were also assessed for the 2 influenza seasons included in the study. RESULTS: There were 1898 subjects. Pneumococcal vaccination was associated with significantly lower risks for pneumonia hospitalizations (adjusted risk ratio [RR], 0.57; 95% confidence interval [CI], 0.38-0.84; P=.005) and for death (adjusted RR, 0.71; 95% CI, 0.56-0.91; P = .008). For the control outcome of all nonpneumonia hospitalizations, rates did not differ significantly between the 2 groups (adjusted RR, 0.91; 95% CI, 0.77-1.07; P= .24). During the influenza seasons included in the study, the benefits of pneumococcal and influenza vaccinations were additive, with an adjusted RR of 0.28 (95% CI, 0.14-0.58; P<.001) for the number of hospitalizations for pneumonia and influenza among persons who had received both vaccinations compared with those who had received neither and an adjusted odds ratio of 0.18 (95% CI, 0.11-0.31; P<.001) for death. Over the 2-year outcome period, pneumococcal vaccination was also associated with direct medical care cost savings. CONCLUSIONS: Pneumococcal vaccination of elderly persons with chronic lung disease was associated with fewer hospitalizations for pneumonia, fewer deaths, and direct medical care cost savings.

Aged↗

The effect of tumor necrosis factor blockade on the response to pneumococcal vaccination in patients with rheumatoid arthritis and ankylosing spondylitis.

OBJECTIVE: To assess the effect of anti-tumor necrosis factor (TNF) alpha therapies on the immunogenicity of pneumococcal vaccination in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: A group of 16 consecutive patients (11 with RA and 5 with AS) treated either with infliximab or etanercept, and a control group of 17 age-matched RA patients treated with disease-modifying medications other than anti-TNF-alpha, received intradeltoid injection with 0.5 mL of pneumococcal vaccine. Pneumococcal polysaccharide (PPS)-specific IgG to 7 vaccine PPS (representing high- and low-prevalence serotypes) was measured by enzyme-linked immunosorbent assay in sera obtained before and 1 month after pneumococcal immunization. RESULTS: One month after vaccination, both groups had significant increases in the geometric mean concentration of capsule PPS-specific antibody and in the mean fold increase in antibody levels to all 7 serotypes, compared with prevaccination levels. However, compared with the control group, the TNF-alpha blockade-treated patients tended to have lower antibody increases for all the serotypes tested except serotype 14. In addition, lower proportions of TNF-alpha blockade-treated patients responded to pneumococcal vaccination compared with patients on other therapies. Similarly, more TNF-alpha blockade-treated patients were poor responders compared with patients not on anti-TNF-alpha treatment. CONCLUSION: Treatment of groups of patients with etanercept or infliximab does not impair their mean antibody responses to pneumococcal vaccination. However, a larger proportion of RA patients may not respond adequately to pneumococcal vaccination once on TNF-alpha blockade therapies. Consequently, pneumococcal vaccination before starting TNF-alpha blockade therapy is recommended.

Adult↗

Clinical practice and public policy for influenza and pneumococcal vaccination of the elderly.

Influenza and pneumococcal vaccines are safe, effective, and cost-effective, but they are not used widely. Organized programs for vaccine delivery can lead to substantial improvements in vaccination rates for the elderly. Adequate reimbursement by Medicare and other third-party payers needs to be supplemented by educational programs to promote influenza and pneumococcal vaccines if the opportunity vaccination presents to improve the health and well-being of elderly persons is to be fully realized.

Aged↗

Immunogenicity of pneumococcal vaccination of patients with cochlear implants.

BACKGROUND: Pneumococcal meningitis is a rare but potentially fatal complication of cochlear implantation. METHODS: A prospective study was conducted of the immunogenicity of pneumococcal vaccination in 174 patients with cochlear implants (CIs). The cohort was divided into groups of patients with impaired hearing due to meningitis (P(1)), cranial malformations (P(2)), or an unknown cause (P(3)) and was stratified by age as follows: <2 years (A(1)), 2-5 years (A(2)), and >5 years (A(3)). We determined immunoglobulin (Ig) levels for IgG subclasses 1-4 and serum concentrations of antibodies against pneumococci before and 4-6 weeks after vaccination. Group A(1) received the 7-valent pneumococcal conjugate vaccine (PCV-7), group A(2) received PCV-7 or the 23-valent pneumococcal polysaccharide vaccine (PPV-23), and group A(3) received PPV-23. RESULTS: IgG, IgM, and IgG1 levels were significantly lower in group P(1), compared with the other patient groups and with historic data for healthy control subjects, suggesting a decreased antibody response. Group P(1) had lower levels of pneumococcal antibodies, compared with groups P(2) and P(3) before vaccination (P<.05, pneumococcal serotypes 4 and 9V). Irrespective of the underlying condition, all patients showed a sufficient antibody response after 1 dose of vaccine. In children 2-5 years of age, PCV-7 was significantly more immunogenic than PPV-23. CONCLUSIONS: PCV-7 should be administered to all CI recipients younger than 6 years and older than 6 years who are at an increased risk for bacterial meningitis. CI recipients with a history of bacterial meningitis should undergo immunological evaluation.

Adolescent↗

Influenza and pneumococcal vaccination of HIV-infected patients: a policy analysis.

OBJECTIVE: To analyze the policy of vaccinating human immunodeficiency virus (HIV)-infected young adults against influenza and pneumococcal infections. METHODS: Transition state model of clinical immune deterioration of HIV infection, published data, and experts' estimates for the uncertain variables. Outcome measures are the number of influenza and pneumococcal infection hospitalizations and deaths prevented over 10 years and cost-effectiveness ratios. PATIENTS: Hypothetical cohort of HIV-infected 30-year-old patients. RESULTS: Although pneumococcal vaccine effectiveness diminishes with advanced HIV disease, the risks of pneumococcal infection rise substantially. Pneumococcal vaccination was therefore found to be a reasonable prevention strategy at all HIV disease stages: few vaccinations are needed to prevent hospitalizations and deaths, and the vaccination strategy is cost-effective. By contrast, influenza incidence is low among young adults, and HIV-related immunodeficiency increases influenza risks only minimally. Because the vaccine is administered yearly, many more vaccinations must be administered and fewer hospitalizations and deaths are prevented than with pneumococcal vaccination. The costs to extend life expectancy are high, and beyond the costs of other prevention strategies for persons with moderate to severe immunodeficiency. CONCLUSIONS: Pneumococcal vaccination is a reasonable prevention strategy for HIV-infected patients at all stages of immunodeficiency. Fewer hospitalizations and deaths are prevented by influenza vaccination, making it a far less cost-effective prevention strategy than pneumococcal vaccination.

AIDS-Related Opportunistic Infections↗

[Pneumococcal vaccination in obstructive lung diseases -- what can we expect?].

Many countries' guidelines recommend pneumococcal vaccination for patients suffering from obstructive airway disease. This paper reviews the literature as to immunogenicity and safety of this immunization. There is no evidence for a negative effect of pneumococcal vaccination on these patients. Only a few data exist on the preventive impact of pneumococcal vaccination as to exacerbations of obstructive airway diseases. Existing studies mostly took up this question as a side aspect. The effect in children and adults appears limited. On the other hand, the pneumococcal conjugate vaccine prevents life-threatening invasive infections in children younger than 5 years, and pneumococcal polysaccharide vaccine protects healthy adults against bacteriaemic pneumonia. Thus, pneumococcal vaccination of patients suffering from obstructive airway disease is recommendable.

Adolescent↗

Introducing a pneumococcal vaccine to an existing influenza immunization program: vaccination rates and predictors of noncompliance.

PURPOSE: Influenza vaccination has been recommended for all elderly people in The Netherlands since 1996, with greater than 80% compliance. It is unknown, however, if the addition of another vaccine to this immunization program will affect compliance. SUBJECTS AND METHODS: General practitioners offered a pneumococcal vaccine together with the yearly influenza vaccination to 3365 patients aged 65 years and older. A questionnaire was then mailed to a stratified sample (n = 972) of these patients. Factors associated with noncompliance with vaccination were assessed using polytomous logistic regression. RESULTS: A total of 2529 patients (75%) received the pneumococcal vaccine and 2812 (84%) received the influenza vaccine. Predictors of noncompliance with the pneumococcal vaccine were perceived lack of recommendation by the general practitioner (odds ratio [OR] = 4.6; 95% confidence interval [CI], 2.6 to 8.3) and fear of local side effects (OR = 2.8; 95% CI, 1.6 to 4.6). Predictors of noncompliance with both vaccinations also included unwillingness to comply with the doctor's advice (OR = 6.1; 95% CI, 2.4 to 15.4), the belief that vaccinations weaken one's natural defenses (OR = 2.7; 95% CI, 1.4 to 5.3) or that influenza is not dangerous (OR = 2.9; 95% CI, 1.5 to 5.4), and the fear of becoming sick from pneumococcal vaccination (OR = 2.9; 95% CI, 1.1 to 7.9). People who felt healthy, found it difficult to visit the doctor's office, had private medical insurance, or were younger than 75 years of age also had a greater risk of not being vaccinated. CONCLUSION: Introducing a pneumococcal vaccine to an existing influenza immunization program resulted in high pneumococcal and influenza vaccination rates. A wider diversity of patient characteristics and attitudes was present when neither vaccination was received.

Aged↗

Accuracy of adult reported pneumococcal vaccination status of children.

PURPOSE: A pneumococcal conjugate vaccine was licensed in 2000 for use in children. To evaluate the accuracy of an adult's recall of children's vaccination status with the pneumococcal vaccine, the authors conducted a cross-sectional survey of adults in Philadelphia County from January to December 2003. METHODS: Subjects were identified by random digit dialing and interviewed regarding the age and vaccination status of all children 6 years old or younger with whom they had significant contact. The gold standard for determining the accuracy of vaccine status reports was the Kids Immunization Database/Tracking System (KIDS) at the City of Philadelphia Department of Public Health. RESULTS: One hundred twenty-two interviews were completed with vaccination data collected on 185 children. One hundred sixty-six children (90%) were matched with records in the KIDS registry. The sensitivity and specificity of adult reported child vaccine status were 0.65 (95% CI, 0.55, 0.74) and 0.47 (95% CI, 0.34, 0.61), respectively. Agreement between adult report and the KIDS registry was 59%. Significant variation in agreement was not found to be related to demographic characteristics of the adult subjects. CONCLUSION: Adult report of the pneumococcal vaccination status of children was found to be relatively inaccurate and did not vary by known demographic characteristics.

Adult↗

Underutilization of pneumococcal vaccine in nursing home in Washington State: report of a serotype-specific outbreak and a survey.

PURPOSE: To describe an outbreak of pneumococcal disease in a Washington state nursing home and to report a survey of pneumococcal vaccine utilization in Washington nursing homes. PATIENTS AND METHODS: Outbreak. Data were collected from nursing home residents' records. Nasopharyngeal cultures were obtained from residents and staff. Survey. Fifty-four randomly selected Washington nursing homes were surveyed about pneumococcal vaccine utilization and policies. RESULTS: Outbreak. Three confirmed and 4 possible cases of pneumococcal disease occurred over 9 days among 94 residents; 5 patients (71%) died. Cases were identified among 6 of 42 residents on 1 wing, compared with 1 of 52 on the other 2 wings (relative risk 7.4, 95% confidence interval 1.0, 398.5). Streptococcus pneumoniae serotype 9V was cultured from the blood of 3 confirmed case-patients and the nasopharynx of 2 of 73 residents. Only 7% of residents had received pneumococcal vaccine, including one case-patient who had received 14-valent vaccine without serotype 9V. Survey. Only 22% of residents were reported to have received pneumococcal vaccine; vaccination status was unknown for 66%. Physician discretion determined pneumococcal vaccination in 49 (91%) nursing homes; 9 (17%) had a written policy. Two major barriers to pneumococcal vaccination were cited: low priority among physicians (43%) and difficulty in determining residents' vaccine history (37%). CONCLUSIONS: A pneumococcal disease outbreak among undervaccinated nursing home residents probably resulted from person-to-person transmission. Pneumococcal vaccine appears to be underutilized in Washington state nursing homes.

Aged↗

Method for ascertaining denominators for evaluation of population coverage with pneumococcal vaccine.

BACKGROUND: Immunization programs may collect numerator data for the estimation of pneumococcal vaccine coverage, but program evaluators do not have appropriate denominator data for estimation of pneumococcal vaccine coverage, particularly among those eligible for vaccine on the grounds of having chronic health conditions. METHODS: We partitioned the Alberta population into 6 mutually exclusive groups, all but one of which met Canadian recommendations for pneumococcal vaccination. Age-sex specific prevalence rates for each group were estimated using data on chronic health conditions from the Alberta over-sample of the 1996 Household component of the National Population Health Survey, from Alberta Health and Wellness rosters of nursing home residents, and from the Alberta Health Care Insurance Plan Stakeholder Registry. We applied these to Alberta Population Projections to estimate the numbers of persons who should be vaccinated. RESULTS: The proportion of persons recommended for vaccination on the grounds of chronic health condition ranged from 1.5% among those aged less than 12 years to 36% among persons aged 80 years or older. The total number of persons recommended for vaccination at mid-year 2000 is estimated to be 638,561 (21.5% of the Alberta population). INTERPRETATION: This methodology provides denominators for the estimation of pneumococcal vaccine coverage and permits monitoring of local and regional progress towards national goals.

Adolescent↗