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Pneumococcal infections in adults vary in severity and incidence is affected by childhood vaccination policy. Here, we try to define the host determinants and the interaction with specific serotypes that result in invasive pneumococcal disease (IPD) before an expected effect of pneumococcal conjugate vaccines. A nationwide active surveillance was initiated on July 2009, at the time of national implementation of PCV7 in Israel. The surveillance included all 27 laboratories and medical centers performing blood cultures in Israel, providing all blood and CSF pneumococcal isolates from persons ≥18y. Capture-recapture method assured that >95% of all cases were reported. IPD outcome and medical history were recorded and isolates were serotyped. Four hundred and sixty IPD cases were reported (annual incidence [/100,000] of 9.25). Incidence increased with age, from 2.6 among 18-34y to 66.8 among ≥85y. The most common diagnosis was pneumonia (72.4%), followed by bacteremia with no apparent focus (20.2%). Case fatality rate increased with age and number of comorbidities (34.5% for ≥75y or those with ≥3 comorbidities vs. 9.2-11.2% among <65y or those with no comorbidities; p=0.015). Variables independently associated with mortality were: age ≥75, chronic renal failure, malignancy, neurosurgery, alcohol abuse, multi-lobar pneumonia and sepsis with no apparent focus. The predominant serotypes in patients 18-49y were 1, 5, 8, 7F and 9V (constituting 56.3% in this age-group vs. 11.9% in ≥75y; p<0.01). The predominant serotypes among patients ≥75y were 3, 19A, 23F and 14 (40.3% of this age-group vs. 12.9% of 18-49y; p<0.01). Overall, PCV7 and PCV13 covered 25.6% and 63.7% of isolates, respectively, and 30.9% and 67.9% of isolates in mortality cases respectively. This nationwide active surveillance provides the baseline incidence, mortality rates and risk group distributions of IPD in adults before expected PCV effect., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Streptococcus pneumoniae serotype 19A is associated with all forms of pneumococcal disease and was the first reported pneumococcal serotype with high-level penicillin and multidrug resistance. While the seven-valent pneumococcal conjugate vaccine (PCV7), which contains serotype 19F, has reduced rates of disease among children and adults, the incidence of disease due to nonvaccine and increasingly drug-resistant serotypes - predominantly serotype 19A - has increased. This review summarizes the published literature to analyze the factors contributing to the emergence of serotype 19A, the diseases associated with this serotype, and the importance of including this serotype in novel pneumococcal conjugate vaccines. A recently approved 13-valent vaccine includes this serotype, and is likely to significantly reduce the burden of disease due to serotype 19A., ((c) 2010 Elsevier Ltd. All rights reserved.)

We aimed to assess the efficacy of a pneumococcal conjugate vaccine against acute otitis media (AOM) positive by pneumolysin-PCR (Ply-PCR). 1662 infants vaccinated with PncCRM or control vaccine using random allocation were followed for AOM up to 24 months of age. When AOM was diagnosed a middle ear fluid sample was obtained for etiological assays. During the per protocol follow-up period the PncCRM vaccine efficacy was 19% against Ply-PCR-positive AOM but only 3% when culture-positive cases were excluded. The data do not support effect of PncCRM on AOM in which only Ply-PCR suggests pneumococcal etiology.

The 23-valent polysaccharide pneumococcal vaccine is currently recommended in elderly and high-risk adults. Its efficacy against invasive pneumococcal disease has been demonstrated, but its effectiveness in preventing pneumonia remains uncertain. This study assessed the clinical effectiveness of vaccination against pneumonia among middle-aged and older adults. We conducted a population-based case-control study including 304 case patients over 50 years old with radiographically confirmed pneumococcal pneumonia (94 bacteremic and 210 nonbacteremic cases) and 608 outpatient control subjects (matched by primary care centre, age, sex and risk stratum). Adjusted odds ratios (ORs) for vaccination were calculated using conditional logistic regression, controlling for underlying conditions. Vaccine effectiveness against all pneumococcal pneumonia was 48% (OR: 0.52; 95% confidence interval [CI]: 0.37-0.73). Vaccination was effective against bacteremic cases (OR: 0.34; 95% CI: 0.27-0.66) as well as nonbacteremic cases (OR: 0.58; 95% CI: 0.39-0.86). Vaccine effectiveness was highest against bacteremic infections caused by vaccine types (OR: 0.24; 95% CI: 0.09-0.66). These findings confirm the effectiveness of the vaccine against invasive disease, but they also support the benefit of vaccination in preventing nonbacteremic pneumococcal pneumonia.

Aims: A cost-effectiveness model was used to estimate the change in disease burden that might be expected if PCV7 was included as part of the routine 3-dose vaccination schedule in Sweden., Methods: An economic model was populated with data from the main clinical PCV7 efficacy trials, demographic data from government sources, surveillance and epidemiologic data from the US and Nordic region, and average treatment costs, considering the impact of disease on the whole national population., Results: The model estimated that PCV7 would prevent 18,856 cases of AOM, 684 of pneumonia, 86 of pneumococcal bacteraemia and 21 cases of pneumococcal meningitis in children <10 years, further 221 cases of IPD would be avoided in older children and adults and 397 cases of pneumonia in adults aged 18-39 years. Annually, 4 childhood (<10 years) deaths and 39 deaths in older children and adults would be prevented, resulting in an annual saving of 632 life years. The reduction of cost for the society was estimated to 27.9 (-205, +160) million SEK. The sensitivity analysis showed that it was most sensitive to the efficacy of the vaccine against AOM, the cost of managing infections and the incidence of all disease., Conclusion: This model demonstrates that implementing a universal vaccine programme in Sweden with PCV7 would be cost-effective with an estimated net reduction of costs for the society.

Unlabelled: Advanced age has been associated with a wide range of defects in both the innate and adaptive immune systems including diminished specific antibody responses that increase the risk of invasive pneumococcal disease (IPD) and limit the effectiveness of vaccines. However, the elderly are a heterogeneous group and measures of overall frailty may be a better indicator of disease susceptibility (or vaccine response) than chronological age alone., Aim: To evaluate the immunogenicity of the 7-valent conjugated pneumococcal vaccine (PCV7) versus 23-valent polysaccharide vaccine (23vPPV) and compare the immune response to four serotypes (4, 6B, 18C and 19F), with respect to age or frailty in an elderly population of previously unvaccinated hospitalized patients., Method: 241 patients aged 60 years and over, recruited between 16 May 2005 and 20 February 2006, were randomised to 23PPV or PCV7 vaccine. We measured Frailty Index (FI), Barthel index and the MiniMental State. Serotype-specific IgG was measured by ELISA at base line and 6 months after vaccination. Antibody responses were defined by the ratio of post-vaccination to pre-vaccination IgG antibody concentration (poor < 2-fold increase, acceptable > or = 2.0 to 3.99-fold and strong > or = 4.0-fold increase)., Results: Pre-immunization IgG was generally low and did not differ significantly by age or frailty. Post-immunization, IgG increased to all four serotypes; acceptable or strong response ranged between 29% for (6B) and 57% for (18C). There was no significant difference between the two vaccine types (23PPV versus PCV7). At 6 months post-vaccination, the highest geometric mean IgG concentrations (GMCs) were seen for serotype 19F and the lowest for serotype 4. Although there was some variation by serotype, responses after vaccination were lowest in the most frail or aged subjects., Conclusions: Pneumococcal vaccines are perceived to offer low protection in the frail elderly, but our study showed that the proportion of this vulnerable population with acceptable responses is encouraging. Frailty, as measured by the Frailty Index, appears to be a better predictor of immune response to pneumococcal vaccines than age alone.

Bacterial clearance and immune responses in a mouse model of pneumonia and a rat model of otitis media following parenteral or mucosal immunisation in both models were compared. Both the immunisation routes were equally effective in inducing bacterial clearance from the lung, upregulated the recruitment of white cells and lead to an increase in the concentration of TNF-alpha, IL-1beta and specific antibody in the bronchoalveolar lavage. Both the routes of immunisation enhanced clearance of bacteria from the middle ear. Parenteral immunisation was most effective overall in enhancing bacterial clearance and recruiting white cells to the middle ear. Both the routes significantly suppressed the levels of TNF-alpha in the middle ear lavage. Mucosal immunisation induced a Streptococcus pneumoniae-specific IgA antibody response. Both the animal models gave highly reproducible disease and provided high levels of sensitivity for testing the efficacy of candidate vaccine antigens. Differences observed in the inflammatory responses require further study.

This paper summarizes the discussion and viewpoints from a recent meeting regarding the use of animal models for pneumococcal protein vaccines. A wide spectrum of workers in this field met to discuss the animal species to be used in models, the approach of passive and active protection, the characteristics of challenge pneumococcal strains, inducing disease syndromes by a variety of routes of challenge, the determination of specific endpoints to assess effectiveness, the correlates of protection and other details of experimental design and analysis. Vaccine regulatory aspects were discussed. The document concludes with a series of questions that remain to be investigated.

The pre-clinical immunogenicity of a combination vaccine containing 13-valent pneumococcal conjugate (13vPnC) vaccine (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F conjugated to CRM197) and nine-valent meningococcal B PorA vaccine (NonaMen; serosubtypes P1.7,16; P1.5-1,2-2; P1.19,15-1; P1.5-2,10; P1.12-1,13; P1.7-2,4; P1.22,14; P1.7-1,1 and P1.18-1,3,6), and any potential immunological interference between pneumococcal and MenB components of the vaccine were evaluated. NIH mice were immunized twice subcutaneously with the vaccines combined in one syringe, or given individually. Combining 13vPnC vaccine with NonaMen vaccine in one syringe had no negative effect on the induced antibody response against any MenB serosubtypes compared to separate injection of the vaccines, and the anti-pneumococcal antibody responses were enhanced. Furthermore, co-administration of the combination vaccine with a combined diphtheria/tetanus/acellular pertussis/inactivated poliomyelitis vaccine/Haemophilus influenzae type b-TT conjugate (DTaP/IPV-Hib) vaccine to New Zealand white rabbits at a different injection site did not affect the anti-pneumococcal polysaccharide and anti-PorA antibody titres. We conclude that no immunological interference was observed by combined administration of pneumococcal conjugate and meningococcal B vaccines in one syringe.

The aim of this study was to investigate the incidence of invasive pneumococcal disease (IPD) in Catalonia. A hospital-based incidence study of the period 1997-1999 was carried out by reviewing the isolations of Streptococcus pneumoniae obtained from normally sterile sites reported by the hospitals that voluntarily participate in the Microbiological Reporting System of Catalonia (MRSC), and those obtained by active retrospective surveillance of cases recorded by microbiology laboratories of the remaining hospitals. Cases of pneumonia were included only if the blood culture was positive. The age, sex and clinical presentation of each patient were recorded. The global incidence of hospital-based IPD was 10.5 per 100,000 persons-year, and was much higher in subjects <2 years of age (59.6) and in those aged > or = 65 years (27.9). In subjects > or = 65 years, bacteremic pneumococcal pneumonias were more frequent in the months from December to March than they were in children <2 years of age (P<0.0001). The global incidence of IPD (10.5 per 100,000 persons-year) is high in Catalonia, greater than that of meningococcal or Haemophilus influenzae invasive disease. In children <2 years, the incidence is nearly six times higher (59.6 per 100,000 persons-year) with pneumonias (rate of 26.2 per 100,000 persons-year) and non-focal bacteremias (rate of 22.1 per 100,000 persons-year) being especially frequent.

Streptococcus pneumoniae is one of the most important human pathogens and improvement of the currently used polysaccharide vaccines is being pursued. We constructed DNA vaccine vectors containing either the full-length psaA (pneumococcal surface adhesin A) or a truncated pspA (pneumococcal surface protein A--pspA') gene. Both constructs showed transient expression of the antigens in vertebrate cells and induced significant antibody response to the pneumococcal antigens in BALB/c mice injected intramuscularly (i.m.). Fusion with an N-terminal cytoplasmatic SV40 T-antigen (CT-Ag), which was previously shown to stabilize poorly expressed antigens through association with Hsp73, also induced anti-PspA antibody response. The induction of antibodies with a low IgG1:IgG2a ratio and elevated gamma interferon (IFN-gamma) production by spleen cells elicited by DNA vaccination indicate preferential priming of Th1 immunity. Since induction of antibodies against both PsaA and PspA was previously shown to correlate with protection against fatal infection with S. pneumoniae and cell-mediated immune responses could contribute to protection, further evaluation of PsaA and PspA as antigens for a DNA vaccine against S. pneumoniae could be promising.

Bacterial meningitis is caused mainly by Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. Haemophilus influenzae type b vaccines have been extremely successful in eradicating the disease from those countries where the vaccine has been introduced. The recent licensure of the conjugated pneumococcal vaccine suggests that this pathogen also will be soon controlled. Consequently, if we succeed in developing effective vaccines against meningococcus, this will enable us to eliminate bacterial meningitis. The global elimination of bacterial meningitis is a goal which, if appropriate resources are applied, can be reached within the first fifteen years of the 21st century.

The burden of pneumococcal disease among elderly people is not widely known. In most countries, the annual incidence of invasive pneumococcal disease in elderly people is most probably >50 cases/100000 persons. Over the past 20 years, only the United States has used pneumococcal vaccine to any appreciable extent, yet among all vaccine-preventable diseases, pneumococcal infections account for the largest proportion of still unprevented illness in Western Europe. Retrospective studies show that vaccination prevents invasive pneumococcal disease. Pneumococcal vaccination appears to be more cost-effective than any other medical intervention commonly used in the elderly. As new data confirm the benefits of vaccination of the elderly against pneumococcal infections, vaccine use has increased in recent years associated with a decline in invasive disease.