Effectiveness of pneumococcal conjugate vaccine.
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Child, Preschool↗
Biomedical subjects
Katherine L O'Brien
Publications and source records attributed to Katherine L O'Brien.
Contributions of Native Americans to the global control of infectious diseases.
For over a half of a century, Native American populations have participated in numerous studies regarding the epidemiology, prevention and treatment of infectious diseases. These studies have resulted in measures to prevent morbidity and mortality from many infectious diseases. The lessons learned from these studies and their resultant prevention or treatment interventions have been applied around the world, and have had a major impact in the reduction of global childhood morbidity and mortality.
Humans↗
Pneumococcal vaccination in developing countries.
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Africa↗
Effect of community-wide conjugate pneumococcal vaccine use in infancy on nasopharyngeal carriage through 3 years of age: a cross-sectional study in a high-risk population.
BACKGROUND: A 7-valent pneumococcal conjugate vaccine (PnCRM7) has been shown to be highly effective in preventing invasive pneumococcal disease. Pneumococcal conjugate vaccines also protect against nasopharyngeal carriage of vaccine serotypes, but the duration of protection against nasopharyngeal carriage is not known. METHODS: A group-randomized efficacy trial of PnCRM7 (vaccine serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) was conducted on the Navajo and White Mountain Apache reservations from April 1997 to October 2000. A group C meningococcal conjugate vaccine was used as the control vaccine. Infants enrolled between 6 weeks and 7 months of age received 3 doses of vaccine 2 months apart and a fourth dose at 12-15 months of age. Vaccinees were enrolled in a nasopharyngeal carriage study from February 2001 to January 2002 to assess the duration of protection against pneumococcal carriage induced by PnCRM7. RESULTS: We included 749 children in the analysis, including 468 children vaccinated with PnCRM7 and 281 children vaccinated with group C meningococcal conjugate vaccine. The median age was 3.3 years (range, 1-7 years), and the median time since last dose of study vaccine was 27 months (range, 12-48 months). Frequencies of overall pneumococcal carriage were similar among PnCRM7 and group C meningococcal conjugate vaccine recipients (63.9% vs. 60.5%, respectively). The absolute frequency of vaccine-type pneumococcal carriage was lower among PnCRM7 recipients (10.3%) than among controls (17.1%; P = .01). This reduction was offset by an increase of nonvaccine-type pneumococcal carriage among PnCRM7 recipients (39.2% vs. 29.8%; P = .01). CONCLUSION: Community-wide PnCRM7 vaccination in infancy reduces the prevalence of vaccine-type carriage and increases the prevalence of nonvaccine-type carriage through at least 3 years of age.
Carrier State↗
Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine.
BACKGROUND: Rotavirus is a leading cause of childhood gastroenteritis and death worldwide. METHODS: We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of live pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at 4-to-10-week intervals in a blinded fashion. Active surveillance was used to identify subjects with serious adverse and other events. RESULTS: The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events. Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent). CONCLUSIONS: This vaccine was efficacious in preventing rotavirus gastroenteritis, decreasing severe disease and health care contacts. The risk of intussusception was similar in vaccine and placebo recipients. (ClinicalTrials.gov number, NCT00090233.)
Administration, Oral↗
Could a single dose of pneumococcal conjugate vaccine in children be effective? Modeling the optimal age of vaccination.
Using incidence rates from CDC's Active Bacterial Core surveillance and immunogenicity data from the Navajo/Apache trial of pneumococcal conjugate vaccine (PCV), we used Markov modeling to predict the optimal age to give a single dose of PCV. Antibody concentration thresholds of 0.35 and 1.0 mcg/ml were considered protective. Our outcome was vaccine serotype-specific invasive pneumococcal disease (IPD) incidence at 24 months. The models predicted the optimal age to vaccinate is 5-7 months with vaccine-induced immunologic memory and 8-10 months without memory. IPD reduction ranged from 15 to 62%, depending on model parameters. A single PCV dose in infants could prevent substantial IPD.
Adolescent↗
Standardized interpretation of paediatric chest radiographs for the diagnosis of pneumonia in epidemiological studies.
BACKGROUND: Although radiological pneumonia is used as an outcome measure in epidemiological studies, there is considerable variability in the interpretation of chest radiographs. A standardized method for identifying radiological pneumonia would facilitate comparison of the results of vaccine trials and epidemiological studies of pneumonia. METHODS: A WHO working group developed definitions for radiological pneumonia. Inter-observer variability in categorizing a set of 222 chest radiographic images was measured by comparing the readings made by 20 radiologists and clinicians with a reference reading. Intra-observer variability was measured by comparing the initial readings of a randomly chosen subset of 100 radiographs with repeat readings made 8-30 days later. FINDINGS: Of the 222 images, 208 were considered interpretable. The reference reading categorized 43% of these images as showing alveolar consolidation or pleural effusion (primary end-point pneumonia); the proportion thus categorized by each of the 20 readers ranged from 8% to 61%. Using the reference reading as the gold standard, 14 of the 20 readers had sensitivity and specificity of > 0.70 in identifying primary end-point pneumonia; 13 out of 20 readers had a kappa index of > 0.6 compared with the reference reading. For the 92 radiographs deemed to be interpretable among the 100 images used for intra-observer variability, 19 out of 20 readers had a kappa index of > 0.6. CONCLUSION: Using standardized definitions and training, it is possible to achieve agreement in identifying radiological pneumonia, thus facilitating the comparison of results of epidemiological studies that use radiological pneumonia as an outcome.
Child, Preschool↗
Delivering pneumococcal vaccine to a high risk population: the Navajo experience.
High rates of preventable diseases such as pneumococcal disease occur among the Navajo despite their universal health insurance through the Indian Health Service. The objective of this study was to determine the proportion of Navajo adults vaccinated with pneumococcal polysaccharide vaccine and to examine key features of vaccination programs of the Navajo Indian Health Service. For this cross-sectional study, medical charts of Navajo patients with vaccine indications were randomly selected and reviewed to determine who had been vaccinated as of January 1, 1999. Among 480 Navajo>or=65 years old, 73% were vaccinated (95% confidence interval [CI]: 69%-77%). Among 111 Navajo 18-64 years old with vaccine indications, 54% were vaccinated (95% CI: 45% -63%). Vaccination programs utilized extensive public health nursing, home visits, standing orders, and "express lane" clinics. In spite of excellent delivery systems and universal healthcare, the proportion of Navajo persons vaccinated was still below the goals for Healthy People 2010 of having 90% of persons>or=65 years old vaccinated and 60% of high-risk persons 18-64 years old vaccinated.
Adolescent↗
Modeling the association between pneumococcal carriage and child-care center attendance.
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Carrier State↗
Epidemiology of invasive Haemophilus influenzae type A disease among Navajo and White Mountain Apache children, 1988-2003.
BACKGROUND: Before the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines, rates of H. influenzae disease among Navajo and White Mountain Apache (WMA) children were among the highest reported worldwide. Routine Hib vaccination has significantly reduced rates of Hib disease in these populations. As Hib disease rates decrease to very low levels, there are concerns that non-type b strains of H. influenzae may emerge as more prevalent causes of invasive disease in children. METHODS: We reviewed population-based, active laboratory surveillance data from the period of 1988-2003 for invasive H. influenzae type a (Hia) disease among Navajo and WMA children aged <5 years. Clinical information on cases was collected by chart review. A sample of Hia isolates from Navajo children was typed by pulsed-field gel electrophoresis (PFGE). RESULTS: During 1988-2003, a total of 76 reported cases of invasive Hia disease occurred among Navajo and WMA children. The overall annual incidence was 20.2 cases per 100,000 population aged <5 years. There was no increase in Hia disease rates after Hib vaccination was introduced. The median age of patients was 12 months. Meningitis (50% of cases) was the most common presentation, followed by pneumonia (27.6%). Two children with Hia disease died. PFGE analysis revealed a limited genetic diversity of Hia strains in this population. CONCLUSIONS: Active surveillance data showed high rates of invasive Hia disease among Navajo and WMA children but no increase in the incidence after Hib vaccination was introduced. The presentation of Hia disease is similar to that of Hib disease in the prevaccine era.
Arizona↗
Epidemiology of invasive Streptococcus pneumoniae among Navajo children in the era before use of conjugate pneumococcal vaccines, 1989-1996.
Streptococcus pneumoniae is the most common cause of invasive bacterial disease among children worldwide. The authors aimed to determine the incidence, clinical characteristics, and serotype distribution of invasive pneumococcal disease (IPD) among Navajo children in the southwestern United States. Active population-based laboratory surveillance for IPD among resident members of the Navajo Nation under 18 years of age was conducted between 1989 and 1996. During this 8-year period, 706 cases of IPD were identified. The rate of disease varied by age, with the highest rate being observed among children aged 6-11 months (727 cases/100,000 person-years), followed by children aged 0-11 months, 0-23 months, and 0-59 months (568, 537, and 272 cases/100,000 person-years, respectively). Among children aged 0-23 months, 60.3% of cases were caused by serotypes in the seven-valent conjugate pneumococcal vaccine (71.5% from 1989-1993 and 58.3% from 1994-1996). Navajo children are at increased risk of IPD in comparison with the general US population. The distribution of disease-causing serotypes is similar to that of many countries in the developing world. Prevention strategies should include the use of licensed pneumococcal protein conjugate vaccine; however, a substantial proportion of disease is caused by nonvaccine serotypes. These data are critical for assessing the impact of these vaccines in this high-risk population.
Age Distribution↗
Potential impact of conjugate pneumococcal vaccines on pediatric pneumococcal diseases.
Children younger than age 2 years have the highest rates of invasive pneumococcal disease and play an important role in its transmission. In the United States, seven pneumococcal serotypes cause approximately 80% of invasive disease and represent approximately 60% of middle-ear isolates in children younger than age 2 years; the majority of penicillin-resistant strains are confined to these same few serogroups. Although unconjugated polysaccharide pneumococcal vaccines have demonstrated effectiveness in preventing invasive disease in adults, these vaccines fail to protect against otitis media or nasopharyngeal carriage and are poorly immunogenic in children younger than age 2 years. A new generation of pneumococcal vaccines has been developed, linking the capsular polysaccharide of seven to 11 serotypes to a protein carrier. The only pneumococcal vaccine approved to date for children younger than age 2 years is a seven-valent conjugate vaccine (PnCRM-7) (Prevnar; Wyeth Vaccines, Pearl River, New York), which contains serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. PnCRM-7 is more immunogenic than the polysaccharide pneumococcal vaccines and is 80-100% effective against vaccine-type invasive disease and 50-60% effective against vaccine-type pneumococcal otitis media. Routine immunization with pneumococcal conjugate vaccines should substantially reduce the morbidity, mortality, and costs associated with pneumococcal disease in children.
Child, Preschool↗
Invasive pneumococcal disease among Navajo adults, 1989-1998.
Compared with white and black persons in the United States, some Native American groups are at increased risk for invasive pneumococcal disease (IPD). To characterize the epidemiology of IPD among Navajo adults, we conducted active surveillance for IPD on the Navajo Nation and reviewed medical records of patients with IPD. For 1997-1998, the annual incidence (cases per 100,000 persons) was 56 for Navajos aged 18-64 years and 190 for Navajos aged > or =65 years. The corresponding rates were 10 and 57 for white and 44 and 82 for black persons in the United States. The case-fatality rate was 14%. Eighty percent of cases were caused by serotypes included in the 23-valent pneumococcal polysaccharide vaccine. Navajo adults have rates of IPD that are 3-5-fold higher than those of the general US population. Additional research is needed to understand the reasons for this elevated risk and to develop prevention strategies.
Adolescent↗
Nasopharyngeal versus oropharyngeal sampling for detection of pneumococcal carriage in adults.
Several studies have shown that nasopharyngeal sampling is more sensitive than oropharyngeal sampling for the detection of pneumococcal carriage in children. The data for adults are limited and conflicting. This study was part of a larger study of pneumococcal carriage on the Navajo and White Mountain Apache Reservation following a clinical trial of a seven-valent pneumococcal conjugate vaccine. Persons aged 18 years and older living in households with children enrolled in the vaccine trial were eligible. We collected both nasopharyngeal and oropharyngeal specimens by passing a flexible calcium alginate wire swab either nasally to the posterior nasopharynx or orally to the posterior oropharynx. Swabs were placed in skim milk-tryptone-glucose-glycerin medium and frozen at -70 degrees C. Pneumococcal isolation was performed by standard techniques. Analyses were based on specimens collected from 1,994 adults living in 1,054 households. Nasopharyngeal specimens (11.1%; 95% confidence interval [CI], 9.8 and 12.6%) were significantly more likely to grow pneumococci than were oropharyngeal specimens (5.8%; 95% CI, 4.8 to 6.9%) (P < 0.0001). Few persons had pneumococcal growth from both specimens (1.7%). Therefore, both tests together were more likely to identify pneumococcal carriage (15.2%; 95% CI, 13.7 to 16.9%) than either test alone. Although we found that nasopharyngeal sampling was more sensitive than oropharyngeal sampling, nasopharyngeal sampling alone would have underestimated the prevalence of pneumococcal carriage in this adult population. Sampling both sites may give more accurate results than sampling either site alone in studies of pneumococcal carriage in adults.
Adult↗
Immunoblot method to detect Streptococcus pneumoniae and identify multiple serotypes from nasopharyngeal secretions.
Conventional culture techniques are limited in the ability to detect multiple Streptococcus pneumoniae serotypes in nasopharyngeal (NP) secretions. We developed an immunoblot (IB) method with monoclonal antibodies (MAbs) to detect S. pneumoniae and to identify serotypes. NP specimens stored in skim milk-tryptone-glucose-glycerol medium were assessed by the IB method and the reference culture method (RM). In the RM, four optochin-sensitive alpha-hemolytic colonies resembling pneumococci were typed by the Quellung reaction. In the IB method, a nitrocellulose membrane blot of surface growth was reacted with a pneumococcal surface adhesion (PsaA) MAb and visualized. Of 47 NP specimens, 32 (68%) were found to be positive and 13 (28%) were found to be negative for pneumococci by both methods; each method alone yielded one positive result. The sensitivity and specificity of the IB method for the detection of pneumococci were 97 and 93%, respectively. To identify serotypes, blots were tested with serotype-specific MAbs (4, 6A, 6B, 9V, 14, 18C, 19F, and 23F). To detect the remaining serotypes, positive serotype-specific replicate blots were compared visually to an original anti-PsaA-positive blot; four unidentified colonies were subcultured and serotyped by the Quellung reaction. Fifty-eight S. pneumoniae-positive NP specimens containing 69 pneumococcal strains (23 serotypes) were tested; 68 (98.6%) of the strains were detected by the IB method, and 66 (95.6%) were detected by the RM. For 11 specimens found to contain two serotypes, both methods detected both serotypes in 7 (63.6%), the IB method alone detected the two serotypes in 3 (27.3%), and the RM alone detected both serotypes in 1 (9%). The IB method identified multiple clones and minor populations of pneumococci in NP secretions. This method is useful for detecting specific serotypes and carriage of multiple serotypes in epidemiologic surveillance and carriage studies.
Antibodies, Bacterial↗
Efficacy and safety of seven-valent conjugate pneumococcal vaccine in American Indian children: group randomised trial.
BACKGROUND: Streptococcus pneumoniae is the main cause of invasive bacterial disease in children aged younger than 2 years. Navajo and White Mountain Apache children have some of the highest rates of invasive pneumococcal disease documented in the world. We aimed to assess the safety and efficacy of a seven-valent polysaccharide protein conjugate pneumococcal vaccine (PnCRM7) against such disease. METHODS: In a group-randomised study, we gave this vaccine to children younger than 2 years from the Navajo and White Mountain Apache Indian reservations; meningococcal type C conjugate vaccine (MnCC) served as the control vaccine. Vaccine schedules were determined by age at enrollment. We recorded episodes of invasive pneumococcal disease and serotyped isolates. Analyses were by intention to treat and per protocol. FINDINGS: 8292 children enrolled in the trial. In the per protocol analysis of the primary efficacy group (children enrolled by 7 months of age) there were eight cases of vaccine serotype disease in the controls and two in the PnCRM7 group; in the intention-to-treat analysis we noted 11 cases of vaccine serotype disease in the MnCC control group and two in the PnCRM7 group. After group randomisation had been controlled for, the per protocol primary efficacy of PnCRM7 was 76.8% (95% CI -9.4% to 95.1%) and the intention-to-treat total primary efficacy was 82.6% (21.4% to 96.1%). INTERPRETATION: PnCRM7 vaccine prevents vaccine serotype invasive pneumococcal disease even in a high risk population. Other regions with similar disease burden should consider including this vaccine in the routine childhood vaccine schedule.
Arizona↗
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↗
The potential indirect effect of conjugate pneumococcal vaccines.
Pneumococcal conjugate vaccines are highly effective in preventing invasive disease in infants and young children, with favorable safety and immunogenicity profiles. These pediatric vaccines have also shown efficacy in reducing cases of non-invasive disease (i.e. otitis media, pneumonia). Recently, pneumococcal conjugate vaccines have demonstrated additional protective qualities that may enhance their use worldwide. For example, they can reduce nasopharyngeal acquisition of vaccine-specific serotypes of Streptococcus pneumoniae, which may in turn reduce the incidence of pneumococcal disease among non-vaccinated individuals; this is termed indirect or herd immunity. Although the emergence of antibiotic-resistant strains has complicated disease management, pneumococcal conjugate vaccines have been shown to protect against pneumococcal disease caused by such strains because most antibiotic-resistant strains are of the serotypes included in these vaccines. Thus, widespread use of these conjugate vaccines may prevent disease by providing both direct and indirect immunity, and may reduce the use of antibiotics and the development of antibiotic resistance worldwide.
Child, Preschool↗