(See the article by Lipsitch et al., on pages 1221-7.)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,). 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.
Field studies of Streptococcus pneumoniae (pneumococci) nasopharyngeal (NP) colonization are hampered by the need to directly plate specimens in order to ensure isolate viability. A medium containing skim milk, tryptone, glucose, and glycerin (STGG) has been used to transport and store NP material, but its ability to preserve pneumococci has not been evaluated. Our objective was to qualitatively and semiquantitatively evaluate the ability of STGG to preserve pneumococci in NP secretions. Entwined duplicate calcium alginate NP swab samples were obtained from children. One swab was plated directly onto a gentamicin blood agar plate; the other was placed in STGG. Growth from the directly plated specimen was compared with growth from an STGG aliquot immediately cultured or stored at ؊70°C for 9 weeks, ؊20°C for 9 weeks, or 4°C for 5 days. Of 186 specimens, 96 (52%) were positive for pneumococci from the direct plating; 94 (98%) of these were positive from the fresh STGG specimen. Pneumococci were recovered from all 38 positive specimens frozen at ؊70°C, all 18 positive specimens frozen at ؊20°C, and 18 of 20 positive specimens stored at 4°C. Recovery of pneumococci after storage of NP material in STGG medium at ؊70°C is at least as good as that from direct plating. Storage at ؊20°C is also acceptable. Storage at 4°C for 5 days is not ideal.Streptococcus pneumoniae (pneumococci) is the most important cause of bacterial otitis media, pneumonia, bacteremia, and meningitis among children worldwide (12,15,17). Pneumococci are also important because the rate of nonsusceptibility to various classes of antimicrobial agents, such as penicillins and cephalosporins, is rising throughout the United States and worldwide (4,18,19). Prevention efforts have been hampered by the lack of a vaccine which is immunogenic for important serotypes in children younger than 2 years of age. A seven-valence pneumococcal conjugate vaccine (Prevnar; Wyeth Lederle Vaccines) which is immunogenic and efficacious in this age group recently has been licensed in the United States for use among children through 9 years of age and is recommended routinely for those under 2 years of age (1, 3, 16). The effect of this and other conjugate pneumococcal vaccines on nasopharyngeal (NP) colonization is a subject of intense investigation.It is well known that pneumococci are spread from person to person via the respiratory route. NP colonization studies have shown that people acquire pneumococci at a young age, carry these organisms for various periods of time, may carry more than one serotype at a time, and transmit these organisms to others with whom they are in close contact (2,5,(9)(10)(11)14). Many studies of the dynamics and ecology of pneumococcal NP carriage, particularly in the setting of new conjugate pneumococcal vaccines, will be performed in settings where microbiologic facilities are not readily available.An optimal medium has not been validated for the transport, preservation, and recovery of pneumococci from NP material. One medium, STGG (skim m...
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 µg/mL, a reliable lower limit of detection of 0.09 µg/mL, and a lower limit of quantification in undiluted serum specimens of 3.0 µg/mL anti-PA IgG. The diagnostic sensitivity of the assay was 97.8%, and the diagnostic specificity was 94.2%. 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.
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.
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.
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-tryptoneglucose-glycerin medium and frozen at ؊70°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.Infection with Streptococcus pneumoniae (pneumococcus) can result in a range of illnesses, including bacteremia, meningitis, pneumonia, otitis media, and sinusitis, which together cause substantial morbidity and mortality worldwide. The ascertainment of pneumococcal colonization is important for many types of studies. Several investigators have demonstrated that nasopharyngeal (NP) sampling is more sensitive than oropharyngeal (OP) sampling for detecting pneumococcal carriage in children (4,8,10,14), although contrary results exist (3). The optimal sampling method for identifying pneumococcal colonization in adults is not clear for several reasons. First, few studies have compared the yields from different sampling sites. Second, in some studies the sampling methods are not clearly specified. Third, the optimal sampling method may vary depending on the type of medium and the microbiologic methods used. Four studies that have compared NP and OP sampling in adults have come to different conclusions (2, 6, 9, 10). To our knowledge, no studies have been published that compared sampling sites when skim milk-tryptone-glucose-glycerin (STGG) medium was used to collect and store specimens. The inoculation of STGG medium is at least as sensitive as direct plating (12) and is a commonly used methodology that can be used under a wide variety of conditions. The objec...
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.
Cryptosporidium causes a disease in infant macaques that is clinically, histologically, and microbiologically indistinguishable from that seen in young children. A reproducible experimental model of cryptosporidiosis has been developed in pigtailed macaques (Macaca nemestrina) and used to studied the infectious dose of oocysts and the effect of inoculum size on severity of disease. Inoculation with either 2 x 10(5) or 10 oocysts via nasogastric tube resulted in clinical enteritis and the fecal passage of large numbers of cryptosporidial oocysts in all four primates studied. The size of the inoculum had no apparent effect on the severity or duration of disease. Rechallenge 2 weeks after resolution of the primary infection demonstrated partial acquired immunity. The small inoculum size coupled with the passage of large numbers of oocysts contributes to the highly contagious nature of cryptosporidiosis among captive primates and may be relevant to the epidemiology and control of cryptosporidiosis in humans.
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