Nasopharyngeal carriage of Streptococcus pneumoniae in Navajo and White Mountain Apache children before the introduction of pneumococcal conjugate vaccine.

BACKGROUND: Infants and children are frequently colonized with pneumococcus. Recent nasopharyngeal acquisition of pneumococcus is thought to precede disease episodes. The increased risk of pneumococcal disease among Navajo and White Mountain Apache populations has been documented. Little is known about the dynamics of pneumococcal carriage in these populations. METHODS: A group randomized, controlled trial of 7-valent conjugate pneumococcal vaccine (PnCRM7, Wyeth) was conducted on the Navajo and Apache reservations. A nasopharyngeal (NP) carriage study was nested in the trial to evaluate the impact of PnCRM7 on carriage. Children <6 years of age had NP swabs collected at enrollment and at 6 and 12 months following enrollment. We analyzed carriage data from children in control vaccine randomized communities to describe the epidemiology of pneumococcal carriage. RESULTS: Of the 410 participants enrolled, 92% were colonized with pneumococcus at least once during the course of the study. Sixty-three percent of NP specimens were positive for pneumococcus. The most common serotypes were 6A, 6B, nontypable, 23F, 14, 19F, 19A, and 9V. Thirty-eight percent of isolates were vaccine serotypes. Age <2 years, male sex, daycare attendance, and having a sibling colonized with pneumococcus were associated with an increased risk of carriage. CONCLUSIONS: The high carriage prevalence among Navajo and Apache children reflects an intense exposure to pneumococcus. The lack of modifiable risk factors for carriage highlights the importance of preventive strategies for disease control.

Indirect effect of 7-valent pneumococcal conjugate vaccine on pneumococcal colonization among unvaccinated household members.

BACKGROUND: Since the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in the United States, rates of invasive pneumococcal disease have decreased in both vaccinated and unvaccinated age groups. Reduction of invasive pneumococcal disease in unvaccinated groups has been attributed to reduced transmission of vaccine-type pneumococci in the community. Understanding the impact of PCV7 on carriage among vaccinated and unvaccinated community members is critical to interpreting, predicting, and understanding the impact of PCV7 on disease. METHODS: A group-randomized, phase III efficacy trial of PCV7 was conducted among southwestern American Indian communities. Meningococcal conjugate vaccine against serogroup C was used as the control. After the trial was unblinded, we conducted a carriage study of participating communities to evaluate the impact of PCV7 on colonization among trial participants and their unvaccinated household members. RESULTS: Adults and unvaccinated children aged <5 years living in households with a PCV7 vaccinee were less likely to be colonized with vaccine-type pneumococci (odds ratio [OR] for adults, 0.57; 95% confidence interval [CI], 0.33-0.99; OR for children, 0.57; 95% CI, 0.26-0.98) than were those living in a household with a control vaccinee. There was no difference for children aged 5-17 years. Decreases in vaccine-type carriage were offset by increases in carriage of nonvaccine types. Among adults living with a trial participant colonized with vaccine-type pneumococcus, those in the households randomized to receive PCV7 were less likely to be colonized with the same serotype than were those in the households randomized to receive the control vaccine (OR, 0.34; 95% CI, 0.11-0.99). CONCLUSIONS: Vaccine-type pneumococcal carriage was lower among adults and unvaccinated children living with a PCV7 vaccinee. This is attributable to reduced exposure and reduced transmission when exposure occurs.

Anticapsular serum antibody concentration and protection against pneumococcal colonization among children vaccinated with 7-valent pneumococcal conjugate vaccine.

BACKGROUND: Pneumococcal conjugate vaccines prevent invasive and noninvasive disease due to infection with vaccine serotypes. Pneumococcal conjugate vaccines also prevent nasopharyngeal acquisition of vaccine serotypes, although the mechanism is incompletely understood. METHODS: An efficacy trial of a 7-valent pneumococcal conjugate vaccine was conducted on the Navajo and White Mountain Apache reservations, located in the Southwestern United States; group C meningococcal conjugate vaccine was the control vaccine. Infants were randomized to receive 7-valent pneumococcal conjugate vaccine or group C meningococcal conjugate vaccine at 2, 4, 6, and 12 months of age. Immunogenicity and nasopharyngeal colonization studies were nested in the efficacy trial. We analyzed the correlation between serotype-specific serum IgG concentration at 7 and 13 months of age and nasopharyngeal acquisition of disease at 12 and 18 months of age, respectively. We adjusted for potential confounders using multivariate logistic regression. RESULTS: Among 203 subjects, we observed 60 acquisitions of vaccine-type pneumococci, including 19 acquisitions of serotype 19F (31.7%), and 17 acquisitions of serotype 23F (28.3%). Among recipients of 7-valent pneumococcal conjugate vaccine, increased serotype-specific serum IgG was associated with a reduction in nasopharyngeal acquisition of serotype 23F (relative risk, 0.53; 95% confidence interval, 0.31-0.93) but was not associated with a reduction in acquisition of serotype 19F (relative risk, 1.07; 95% confidence interval, 0.57-2.03). Among group C meningococcal conjugate vaccine recipients, serotype-specific serum IgG was not associated with a reduction in nasopharyngeal acquisition for either serotype. CONCLUSION: An increase in serum antibody concentration was associated with reduced acquisition of serotype 23F pneumococcus (but not with reduced acquisition of serotype 19F pneumococcus) among recipients of 7-valent pneumococcal conjugate vaccine. Differences in antibody concentration, in the functional characteristics of antibody, or in antibody kinetics during infancy may account for differences in carriage protection.

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.

Effect of pneumococcal conjugate vaccine on nasopharyngeal colonization among immunized and unimmunized children in a community-randomized trial.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) prevent vaccine serotype (VT) invasive disease; nonvaccine serotype (NVT) disease increases modestly. The impact of PCV on nasopharyngeal (NP) colonization is essential to understanding disease effects. METHODS: We conducted a community-randomized controlled trial with catch-up vaccination through age 2 years investigating the effect of 7-valent PCV (PnCRM7) on NP colonization among American Indian infants and their unvaccinated contacts. Infants receiving blinded vaccine at 2, 4, 6, and 12-15 months of age had NP cultures obtained at age 7, 12, and 18 months. Serotype-specific colonization was detected by immunoblot. RESULTS: We enrolled 566 vaccinated and 286 unvaccinated children from 511 households and collected 5157 specimens, of which 3525 (68.4%) had pneumococcus. PnCRM7 vaccinees were less likely to be colonized with VT (odds ratio [OR], 0.40 [95% confidence interval {CI}, 0.23-0.67]) but were more likely to be colonized with NVT pneumococci (OR, 1.67 [95% CI, 1.02-2.78]). PnCRM7 vaccinees were less densely colonized with VT strains than control vaccinees (OR, 0.61 [95% CI, 0.38-0.99]). Day care-attending unvaccinated children in PnCRM7 communities were less likely to have VT colonization than those in control communities (OR, 0.27 [95% CI, 0.07-1.07]). CONCLUSIONS: PnCRM7 reduces the risk of VT acquisition and colonization density but increases the risk of NVT acquisition among vaccinees and their household contacts.

Streptococcus pneumoniae and Haemophilus influenzae type B Carriage, Central Asia.

A study of children was conducted in 3 Central Asian Republics. Approximately half of the Streptococcus pneumoniae isolates were serotypes included in available vaccine formulations. Approximately 6% of children carried Haemophilus influenzae type b (Hib). Using pneumococcal and Hib conjugate vaccines may decrease illness in the Central Asian Republics.

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.

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.

Specific, sensitive, and quantitative enzyme-linked immunosorbent assay for human immunoglobulin G antibodies to anthrax toxin protective antigen.

The bioterrorism-associated human anthrax epidemic in the fall of 2001 highlighted the need for a sensitive, reproducible, and specific laboratory test for the confirmatory diagnosis of human anthrax. The Centers for Disease Control and Prevention developed, optimized, and rapidly qualified an enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) antibodies to Bacillus anthracis protective antigen (PA) in human serum. The qualified ELISA had a minimum detection limit of 0.06 micro g/mL, a reliable lower limit of detection of 0.09 micro g/mL, and a lower limit of quantification in undiluted serum specimens of 3.0 micro g/mL anti-PA IgG. The diagnostic sensitivity of the assay was 97.8%, and the diagnostic specificity was 97.6%. A competitive inhibition anti-PA IgG ELISA was also developed to enhance diagnostic specificity to 100%. The anti-PA ELISAs proved valuable for the confirmation of cases of cutaneous and inhalational anthrax and evaluation of patients in whom the diagnosis of anthrax was being considered.