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PubMed2005

Invasion of endothelial cells by Neisseria meningitidis requires cortactin recruitment by a phosphoinositide-3-kinase/Rac1 signalling pathway triggered by the lipo-oligosaccharide.

Type-IV-pilus-mediated adhesion of Neisseria meningitidis (also known as meningococcus) to human endothelial cells induces the formation of membrane protrusions leading to bacterial uptake. We have previously shown that these protrusions result from a Rho- and Cdc42-dependent cortical actin polymerization, and from the activation of the ErbB2 tyrosine-kinase receptor and the Src kinase, leading to tyrosine phosphorylation of cortactin. We report here that N. meningitidis mutants expressing a deglycosylated lipo-oligosaccharide are poorly invasive. These mutants show structurally altered actin polymerization. Moreover, although they efficiently recruit and activate ErbB2 and Src, these mutants are defective in the recruitment and phosphorylation of cortactin. We demonstrate that phosphorylated cortactin controls the cortical actin polymerization, which leads to membrane protrusion formation. In addition, we show that cortactin recruitment is dependent on the activation of a phosphoinositide-3-kinase/Rac1-GTPase signalling pathway, which is required for actin polymerization and internalization of N. meningitidis, and is not activated by the mutant strains. Altogether, these results define a new role for the lipo-oligosaccharide in triggering a phosphoinositide-3-kinase/Rac1 signalling required to elicit an efficient uptake of N. meningitidis in non-phagocytic cells.

Actin Cytoskeleton↗

PubMed1996

Serum antibodies against haemophilus influenzae type b and tetanus at 2.5 years of age: a follow-up of 2 different regimens of infant vaccination.

In 1990-91 we compared 2 Haemophilus influenzae type b (Hib) conjugate vaccines and 2 different regimens of tetanus vaccination, by vaccinating 142 Swedish infants at ages 3, 5, and 12 months, with either PRP-T (the capsular polysaccharide of Hib conjugated to tetanus toxoid) + D (diphtheria toxoid), or with PRP-OMP (PRP conjugated to an outer membrane complex of meningococcus group B) + DT (diphtheria-tetanus toxoid). In this follow-up, antibodies against Hib and tetanus were analyzed in sera from 133 of the children at the age of 2.5 years. Hib antibodies (> or = 0.06 micrograms/ml) were found in 99% of the children of both groups, but 93% of the PRP-T vaccinees had maintained Hib antibodies > or = 0.15 micrograms/ml, as compared with 80% of the PRP-OMP vaccinees (p < 0.05). In 1992, the batch of PRP-OMP was reported to have questionable immunogenicity. Tetanus toxoid (T) antibodies (> or = 0.01 IU/ml) were found in all sera from both groups. All sera with T antibodies < 0.1 IU/ml showed tetanus toxin neutralizing activity. However, only 75% of children vaccinated with PRP-T had T antibodies > or = 0.1 IU/ml, as compared to 97% of children vaccinated with DT (p < 0.001). In conclusion, Hib and tetanus antibodies were well maintained 18 months after primary vaccination, also in the group vaccinated with the batch of PRP-OMP of somewhat low immunogenicity and in the group of infants receiving their primary tetanus vaccination only by the carrier protein of PRP-T.

Antibodies, Bacterial↗

PubMed1998

[Factors affecting Neisseria meningitidis and Neisseria lactamica carrier state].

Invasive meningococcal diseases have become in the Czech Republic since 1993 a serious epidemiological and clinical problem due to a clonus which was not present previously: Neisseria meningitidis C:2a:P1.2,P1.5, ET-15/37. In 1996 a trial was conducted focused on the problem how this altered epidemiological and clinical situation is reflected in carriership of Neisseria meningitidis and Neisseria lactamica in the healthy population. Two age groups were followed up which were most severely affected by the new clonus of the meningococcus: 15-19 years (410 subjects) and 1-4 years (116 subjects). The trial was implemented in Olomouc where in 1993 the new epidemiological situation of the incidence of the invasive meningococcal disease was so serious that targeted vaccination was introduced. Of 116 children in the age group from 1-4 years in none Neisseria meningitidis was detected, in 9 Neisseria lactamica was found (7.7%). On repeated examination of children with a positive cultivation of Neisseria lactamica after two weeks in none Neisseria meningitidis nor Neisseria lactamica were found. Of 410 subjects in the age group from 15-19 years in none Neisseria lactamica was detected and in 35 Neisseria meningitidis (8.5%). Examinations were repeated after two weeks in 33 carriers: in 31 Neisseria meningitidis was again cultivated. Analysis of factors influencing carriership revealed in Neisseria lactamica two factors in young children which significantly promote this carriership: cold and close contact/kissing. A risk factor at the limit of significance are frequent respiratory diseases. In the carriership of Neisseria meningitidis in 15-19 year-old subjects six factors were revealed which promote carriership. A significant risk factor is close contact/kissing, the existence of partnership, participation in activities of the "disco" type, living in a town, flats in the centre of the town. Effort is a risk factor at the limit of significance.

Adolescent↗

PubMedDate not supplied

[Analysis of the management of the vaccination campaign in 1996-1997 against meningococcus C in Galicia].

This paper describes the process to design and plan a vaccination campaign against group C N. Meningitidis developed in the Autonomous Community of Galicia between December 9, 1996 and January 31, 1997. We also analyse the results of this process in terms of management results, vaccine coverage and preliminary estimates of effectiveness. A Work group was established, made up of professionals in charge of different intervention areas. A person was designated in charge of the whole campaign and a follow-up and information system was created. The work plan consisted of daily meetings for follow-up, co-ordination and task distribution; and periodical meetings with primary health care and peripheral public health coordinators. Strategies of implantation--in order to make sure the campaign accessibility and acceptability; of budget and of communication with health workers, inhabitants and mass media were developed. Up to 100 tasks were identified to develop the technical information and logistic activities: mailings, meetings, leaflets, ...; purchasing of 584.980 doses of vaccine, supplying to 715 vaccination points (1040 deliveries); problem solving and intervention recording. A vaccination coverage of 85% was achieved, with notification of 8 adverse reactions and 6 errors in the administration of the vaccine (34 children affected). The strategy chosen for the design and planning of the campaign has proven to be effective and valid and sufficient to achieve the final goals, in due time and without problems of misinformation, shortage of vaccine or lack of participation of professionals or people. Mistakes due to incorrect administration of the vaccine, management problems, rupture of the cold chain or recording failures were minimal and accidental.

Health Education↗

PubMedDate not supplied

[Results of a study on the under-detection of meningococcus in vaccinated subjects in Galicia].

BACKGROUND: On the basis of active surveillance and the monitoring of Meningococcal Disease (MD) following the vaccination campaign carried out in Galicia, it was observed that the proportion of isolations of the serogroups responsible for the disease among individuals suspected of Meningococcal Disease (SMD) who had been vaccinated was lower than among unvaccinated individuals. In view of this situation, a study was made in order to determine whether in the origin of those SMDs that were not isolated, we would find N. Meningitidis serogroup C, and to quantify the significance of the sub-detection of same. METHODS: For this purpose, and during the period under study (from the 26th week of 1997 to the 14th week of 1999), blood and cephalorachidian fluid samples were taken from the SMDs without isolation for their study with C protein reagent for type and serogroup. The analysis of the samples was performed by the microbiology laboratory of the Clinical Hospital of Santiago de Compostela. RESULTS: Of the 120 cases notified during the period under study, 65 were analysed by C protein reagent (38 vaccinated and 27 unvaccinated), with a positive reading for N. meningitidis in 65% (42 samples) 74% in vaccinated individuals and 52% in unvaccinated. By estimating, on the basis of the cases studied, the results for the total, and excluding the C protein reagent negative cases, we find that, for serogroup C, in only 27% of the cases occurring in vaccinated individuals was it possible to isolate it, in comparison with 80% in the case of unvaccinated subjects (p < 0.0001). These percentages are, in the case of serogroup B, 59% and 71%, respectively, a difference which is not statistically significant. CONCLUSIONS: The vaccine brought about an true sub-detection of serogroup C meningococci in the vaccinated cases.

Adolescent↗

PubMed2006

Distribution of epidemic antibiotic-resistant pneumococcal clones in Scottish pneumococcal isolates analysed by multilocus sequence typing.

Sequence types of pneumococci isolated in Scotland between 1996 and 2003 were compared with those of globally prevalent antibiotic-resistant clones. Multilocus sequence typing was performed on 252 invasive pneumococcal isolates referred to the Scottish Meningococcus and Pneumococcus Reference Laboratory. Isolates were not preselected for antimicrobial resistance, patient age or disease caused. Sequence types were compared with globally significant antimicrobial-resistant clones identified by the Pneumococcal Molecular Epidemiology Network (PMEN). Sequence types identical with three of the 26 PMEN clones were present in the Scottish collection; the clones were the Spain(9V)-3 clone (sequence type 156, seven isolates), the England(14)-9 clone (sequence type 9, eight isolates) and the Utah(35B)-24 clone (sequence type 377, one isolate). Many Scottish isolates related to PMEN clones had lower antimicrobial MICs than those described for the corresponding PMEN type strain. A number of single- (SLVs) and double-locus variants (DLVs) were present. Fifteen SLVs related to PMEN sequence types 37, 67, 90, 81, 156, 236 and 377 were detected. The collection contained 10 DLVs related to PMEN sequence types 37, 156, 173 and 338. The majority of SLVs and DLVs were penicillin- or erythromycin-sensitive variants of the resistant PMEN type strains. Capsule switching in isolates related to the PMEN clones was also detected. The highest levels of penicillin resistance were detected in sequence type 320 (serotype 19F), which is not a PMEN clone. These data suggest that PMEN clones are not widely distributed in disease-causing isolates in Scotland.

Anti-Bacterial Agents↗

PubMed2002

Safety and immunogenicity of meningococcus serogroup C conjugate vaccine administered as a primary or booster vaccination to healthy four-year-old children.

BACKGROUND: Meningococcal C conjugate (Men C) vaccines have been routinely used in the UK since November, 1999. Little information exists regarding antibody persistence or immunologic memory after infant vaccination or response to a first dose at 4 years. METHODS: Ninety-five children immunized at 2, 3 and 4 months of age with 0 or 3 doses of Men C vaccine, boosted with Men C or meningococcal A/C polysaccharide vaccine at 12 months, received a single dose of Men C vaccine at 4 years; 103 age-matched controls were recruited. Pre- and postvaccination Men C IgG (enzyme-linked immunosorbent assay) antibody titers and serum bactericidal activity (SBA) were measured. Safety data were also collected. RESULTS: Baseline SBA titers of > or =1/4 were observed in 87% of children after at least 3 doses of Men C vaccine in infancy compared with 21% of controls. Reciprocals of postvaccination SBA geometric mean titers in those with four prior doses [3803 (95% confidence interval 3489, 4146)] were significantly higher than controls [33 (95% confidence interval 20, 55)] ( < 0.001). Memory was attenuated by the 12-month meningococcal A/C polysaccharide booster [734 (95% confidence interval 484, 1115)] ( < 0.001). All children had IgG responses to a first dose of Men C vaccine, 80% achieving SBA titers of > or =1/4 (77% > or =1/8). The vaccine was safe and well-tolerated. CONCLUSION: Infant immunization with Men C produced persistent antibody and immunologic memory at 4 years. All children made IgG antibodies after a first dose at this age, with 80% showing bactericidal activity. Clarification of the best measures of Men C vaccine-induced protection is needed, through correlation of immunogenicity data such as this with UK vaccine efficacy estimates.

Antibodies, Bacterial↗

PubMed2004

[Meningococcal sepsis in pediatrics. Parameters associated with poor outcome].

BACKGROUND: Mortality due to meningococcal sepsis continues to be extremely high. Patients with a poor prognosis require aggressive therapy and should be identified early. OBJECTIVE: To investigate the clinical and biological factors associated with poor outcome. PATIENTS AND METHOD: Seventy-one children aged 2 months to 13 years with meningococcal sepsis were studied. Inclusion criteria were meningococcus isolation in cultures or characteristic clinical features with purpuric exanthema. METHODS: A correlational descriptive study was performed. In all patients we evaluated the Pediatric Risk of Mortality (PRISM), the Glasgow Scale for Meningococcal Sepsis (GSMS), polymorphonuclear (PMN) count and prolactin (PRL), leptin (LPT) and C-reactive protein (CRP) levels. RESULTS: Fourteen children (19.7 %) died. Death was associated with multiple organ dysfunction syndrome (MODS) (p = 0.0001), high GSMS and PRISM scores (p = 0.0001) and to a lesser extent with shock (p = 0.01). In patients who died, the determinations showing greatest alteration at admission were PRL levels (p = 0.0009) and PMN count (p = 0.0005). CRP levels were not associated with differences in mortality but were high in patients with shock (p = 0.008). Children with high body weight percentiles were at greater risk of death and showed higher levels of PRL, PCT (p = 0.006) and LPT (p = 0.006), without differences in GSMS or PRISM scores. Age did not influence mortality or PRL levels but did influence GMSM and PRISM scores and PMN and CRP levels. These differences disappeared after the age of 2-3 years. In patients with MODS or shock, the only differences found were reduced PMN count (p = 0.0001) and elevated PRL levels (p = 0.0001). CONCLUSIONS: In meningococcal sepsis, death is more frequent in children with high body weight percentiles. Moreover, these children present elevated PRL and LPT levels, although whether these variables act independently remains to be elucidated.

Adolescent↗

PubMedDate not supplied

[Acute meningococcemia in a 4-month-old infant].

INTRODUCTION: What causes meningococcial diseases (MD) is a Gramm-negative diplococcus Neisseria meningitidis (meningococcus). Most frequently it manifests itself in the form of meningitis and meningococcemia. The mortality rate of those suffering from MD has not significantly changed for three decades and ranges from 7% to 19%, and for meningococcemia from 18% to 53%. According to the data presented by domestic authors, of the total of the diseased with bacterial meningitis 75% are children with mortality rate from 6% to 15%. Severe forms of meningococcemia sometimes have extremely rapid development and lethal outcome within a few hours. Key elements for establishing the diagnosis of meningococcemia are presence of hemorrhagic rash with high fever, loss of interest in the environment, loss of consciousness and paleness. CASE REPORT: The boy was admitted to hospital as an emergency case on 29 December 1988 at 11:45. The disease manifested abruptly the day before. He burst into tears easily, would take very little food and in the evening his temperature rose T degree 40.8 degrees C. Before midnight, in the village he was given injections of: lincomycin 300 mg and lasdol 250 i.m. During admittance the infant was agitated, kept moaning. His skin was pail gray with dot-like and spot-like hematoma which were more numerous and intense on the left ear, lower part of the body, scrotum and legs. The infant breathed heavily and fast (FR: 100/min) Cardiologist's finding showed: tahicardia over 200/min, buffled tones, gallop rhythm, pulsating neck veins and edema point to acute heart failure. Large fontanelles remained swollen even after lumbar puncture (LP) and extraction of 15 ml of clear cerebro-spinal fluid. Soon after admittance the boy stopped moaning but didn't cry when pricked and slipped deeper into coma. During the third hour of treatment generalized convulsions began which lasted approximately 10 minutes and stopped after i.v. administered diazepam. The boy remained in coma the second day in lethargy and with swollen fontanelles on the third day, so the first subdural puncture was then performed bilaterally. On that occasion only from the right side 8 ml of reddish liquid was obtained. Right after he was admitted we began permanent transfusion, which lasted 17 days. On the first day he received fresh blood transfusion. He was administered benzinpenicilline, chloramphenicol-succinate, lanatoside, human albumins, dexamethasone.... Blood oxygenation was carried out in the first few days of illness during the exhibited cardio-respiratory failure. DISCUSSION: Among risk factors, which contribute to occurrence of meningococcemia, is also artificial infant food. The reported boy was incorrectly fed with overdiluted cow milk. That and apparent hemostasis brake-down only worsened anemia and increased susceptibility to infections. Although LP was performed when the boy was admitted and the nutritious foundation was soaked with cerebro-spinal fluid, no bacteria were isolated or their presence confirmed in cerebro-spinal fluid colored after Gramm's method, because the child was given linkomycin the previous night. CONCLUSION: On the basis of clinical findings, hemorrhagic rush, convulsions, coma and acute heart failure as well as the laboratory findings it was concluded that it was a case of severe meningococcemia, meningitis and subdural effusion. Listed therapy and six subdural punctures led to full recovery of the patient. Further examination by a pediatrician and a psychologist eliminated the possibility of mental deficiency. The boy is now a good fifth grade elementary school pupil.

Acute Disease↗

PubMedDate not supplied

[Meningococcal disease in Spain, 1990-1997. Change in its epidemiological pattern].

BACKGROUND: In Spain, the presentation of meningococcal disease in the 1980s was closely linked to the predominance of N. Meningitidis serogroup B. This situation changed at the beginning of the 1990s, observing a growing trend of serogroup C strains in the isolation procedures carried out in some areas of the country, together with an increase in the incidence of the disease starting in the 1995-1996 season. The purpose of this study is to characterise the epidemiological pattern of meningococcal disease in Spain during the 1990-97 season and, in particular, where the disease was caused by the phenotype C:2b:P1.2.5 in this period of etiological change. METHODS: Retrospective study of the cases of meningococcal disease in Spain, with the exception of the Autonomous Communities of Andalusia, Cantabria, Madrid, Basque Country and Valencia, between 1990-1997. The epidemiological data were obtained from the Compulsory Disease Reporting system, through individualised notification of cases, and the microbiological data from the Meningococcus Reference Laboratory of the National Microbiology Centre. RESULTS: The incidence of meningococcal disease in the period studied, 1990-1997, was 3.81 x 10 - 6 person-years, increasing by 0.1851 cases per 100,000 inhabitants per year. Starting in 1995, the incidence caused by serogroup C practically tripled with respect to the preceding period, with a rate of incidence in 1997 of 2 cases per 100,000 inhabitants. This increase was to a large extent due to the emergence of the phenotype C:2b:P1.2,5, which in that same year registered an incidence of 1 case per 100,000 inhabitants. The increase in incidence affected all age groups, but was particularly significant in the 5-19 year-old group (annual rate of growth: 13.3%; P < 0.001). It was also found that there was an increase in the number of outbreaks reported and cases associated to them. The overall mortality rate was 7.7% (95% confidence interval: 7.0-8.4), and the mortality associated with the phenotype C:2b:P1.2.5 was significantly higher than that of the serogroup B chosen as reference (odds ratio: 1.69; 95% CI: 1.05-2.71), following adjustment for age, sex, clinical form and year. CONCLUSIONS: The pattern of meningococcal disease in the territory studied, during 1990-1997, was characterised by an increase in the incidence of serogroup C, particularly the emerging phenotype C:2b:P1.2,5. Together with this increase, a displacement of the incidence to higher age groups was observed, together with a tendency towards temporospatial aggregations of cases and an increase in the mortality associated with the new phenotype. This pattern is characteristic of epidemic situations of meningococcal disease caused by serogroup C.

Adolescent↗

PubMed1995

Assessment of the direct effectiveness of BC meningococcal vaccine in Rio de Janeiro, Brazil: a case-control study.

BACKGROUND: Meningococcal disease is still a serious public health problem in many countries. A vaccine produced by Cuba was the first product against B meningococcus available on a large scale. In an attempt to control the increasing incidence of this serogroup in greater Rio de Janeiro, Brazil, the vaccine was used in 1990 in children aged 6 months-9 years. About 1.6 million children were vaccinated. METHODS: In order to assess the direct effectiveness of the vaccine in preventing disease, we conducted a case-control study during the first year after vaccination. Using a hospital-based census, we selected all children hospitalized with meningococcal disease and sampled the control group among children hospitalized with other types of meningitis. Vaccine effectiveness was estimated from the relationship, 1-OR, where OR (odds ratio) was the exponential of the logistic regression coefficient for the association between meningococcal disease and previous vaccination. RESULTS: A total of 275 cases and 279 controls were selected between September 1990 and October 1991. The summary adjusted measure of protection against serogroup B was 54% (95% confidence interval [CI]: 20-74%). Estimated protection varied among different age strata and place of residence, being high among children aged > or = 4 years, 71% (95% CI: 34-87%), and among those who lived in the City of Rio de Janeiro, 74% (95% CI: 42-89%). CONCLUSIONS: The results suggest that the vaccine produced by Cuba may offer protection against serogroup B meningococcal disease, but its effects may not be homogeneous.

Age Distribution↗

PubMed2000

Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group.

OBJECTIVE: To determine the efficacy, safety and immunogenicity of the heptavalent CRM197 pneumococcal conjugate vaccine against invasive disease caused by vaccine serotypes and to determine the effectiveness of this vaccine against clinical episodes of otitis media. METHODS: The Wyeth Lederle Heptavalent CRM197 (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a double blind trial; 37,868 children were randomly assigned 1:1 to receive either the pneumococcal conjugate vaccine or meningococcus type C CRM197 conjugate. The primary study outcome was invasive disease caused by vaccine serotype. Other outcomes included overall impact on invasive disease regardless of serotype, effectiveness against clinical otitis media visits and episodes, impact against frequent and severe otitis media and ventilatory tube placement. In addition the serotype-specific efficacy against otitis media was estimated in an analysis of spontaneously draining ears. RESULTS: In the interim analysis in August, 1998, 17 of the 17 cases of invasive disease caused by vaccine serotype in fully vaccinated children and 5 of 5 of partially vaccinated cases occurred in the control group for a vaccine efficacy of 100%. Blinded case ascertainment was continued until April, 1999. As of that time 40 fully vaccinated cases of invasive disease caused by vaccine serotype had been identified, all but 1 in controls for an efficacy of 97.4% (95% confidence interval, 82.7 to 99.9%), and 52 cases, all but 3 in controls in the intent-to-treat analysis for an efficacy of 93.9% (95% confidence interval, 79.6 to 98.5%). There was no evidence of any increase of disease caused by nonvaccine serotypes. Efficacy for otitis media against visits, episodes, frequent otitis and ventilatory tube placement was 8.9, 7.0, 9.3 and 20.1% with P < 0.04 for all. In the analysis of spontaneously draining ears, serotype-specific effectiveness was 66.7%. CONCLUSION: This heptavalent pneumococcal conjugate appears to be highly effective in preventing invasive disease in young children and to have a significant impact on otitis media.

Bacterial Vaccines↗

PubMed2003

Effect of a nonavalent conjugate vaccine on carriage of antibiotic-resistant Streptococcus pneumoniae in day-care centers.

BACKGROUND: In the developed societies, day-care centers (DCCs) play an important role in the spread of antibiotic-resistant pneumococci both within the facility and from the facility to the community. This study was conducted to determine the effect of a nonavalent pneumococcal conjugate vaccine (PCV-9) on the carriage of antibiotic-resistant pneumococci in the DCC. SUBJECTS AND METHODS: Healthy DCC attendees ages 12 to 35 months were randomized to receive either PCV-9 or a control vaccine (conjugate meningococcus C vaccine) in a double blinded manner. Nasopharyngeal Streptococcus pneumoniae cultures were obtained from each subject before vaccination, monthly during the first year of follow-up and every 2 to 3 months during the second year of follow-up. For each isolate the serotype and antibiotic susceptibility were determined. RESULTS: A total of 132 and 130 evaluable toddlers received either PCV-9 or the control vaccine, respectively. In total 3748 cultures were obtained, of which 2450 (65%) were positive for S. pneumoniae. The resistance rates to penicillin, trimethoprim-sulfamethoxazole and erythromycin were 36, 35 and 16%, respectively. Resistance rates to > or =1 and > or =3 antibiotic categories were 52 and 9%, respectively. Antibiotic resistance was found mainly in the 5 serotypes included in the pneumococcal conjugate vaccines (6B, 9V, 14, 19F and 23F) and in 2 related serotypes (6A and 19A). In the vaccinated group a clear and significant reduction of the carriage rate of the serotypes included in the vaccine and the related serotype 6A as well as an increase in the carriage rate of the serotypes not included in the vaccine were observed. In parallel a significant decrease in carriage rate of antibiotic-resistant pneumococci was observed. The reduction of carriage of antibiotic-resistant pneumococci was seen in all age windows but was greater in the age window <36 months. CONCLUSIONS: The carriage rate of antibiotic-resistant S. pneumoniae, including multiply resistant S. pneumoniae, in DCC attendees is high. Pneumococcal conjugate vaccines seem to be an important tool for reducing the carriage rate of antibiotic-resistant pneumonia in DCCs.

Anti-Bacterial Agents↗

PubMed2003

Vaccination of day-care center attendees reduces carriage of Streptococcus pneumoniae among their younger siblings.

AIM: We conducted a study to determine whether administration of a pneumococcal conjugate vaccine to toddlers attending day-care centers (DCCs) could prevent acquisition of Streptococcus pneumoniae of the vaccine serotypes (VT) by their younger siblings. METHODS: In a double blind study, 262 DCC attendees ages 12 to 35 months were randomized to receive a 9-valent pneumococcal conjugate vaccine (PnCRM9; n = 132), or a control vaccine (meningococcus C vaccine; n = 130). It was planned to follow the groups for 2 years with monthly nasopharyngeal pneumococcal cultures during the first follow-up year and every 2 months during the second year. Forty-six younger siblings of the above described children, age <18 months (23 siblings of the PnCRM9 recipients and 23 of the controls), were also enrolled, and nasopharyngeal cultures were obtained monthly until the children reached the age of 18 months or started to attend DCC, if before the age of 18 months. Pneumococcal isolates were serotyped and tested for antibiotic susceptibility. RESULTS: Of the 3748 cultures obtained from the DCC attendees, 2450 (65%) were positive for S. pneumoniae. Of 306 cultures obtained from the younger siblings, 151 (49%) were positive. Among the PnCRM9 recipients, cultures were significantly less frequently positive for the VT S. pneumoniae than among the controls (13% vs. 21%, respectively; P < 0.001). The same pattern was seen in the younger siblings of PnCRM9 recipients vs. the siblings of controls (21% vs. 34%, respectively; P = 0.017). The reverse trend was seen for non-VT strains in both the DCC attendees (44% vs. 34%, respectively; P < 0.001) and their younger siblings (19% vs. 13%, respectively; P = 0.15). There was a significant decrease in the carriage rate of antibiotic-resistant S. pneumoniae in both the PnCRM9 recipients and their younger siblings. The relative risks (and 95% confidence intervals) to carry S. pneumoniae penicillin-nonsusceptible, resistant to > or =1, > or =2 and > or =3 antibiotic categories among younger siblings of PnCRM9 recipients vs. siblings of controls were 0.47 (0.31 to 0.70), 0.49 (0.33 to 0.71), 0.46 (0.30 to 0.73) and 0.49 (0.21 to 1.17), respectively. When acquired, VT and antibiotic-resistant S. pneumoniae were carried for a significantly shorter period of time among siblings of PnCRM9 recipients than in siblings of controls. CONCLUSION: The marked effect of PnCRM9 administration to DCC attendees on carriage of VT and antibiotic-resistant S. pneumoniae among their younger household close contacts demonstrates a herd effect of the vaccine.

Analysis of Variance↗