Pre-pneumococcal Conjugate Vaccine Research Articles

Unique Features of Hospitalized Children with Alveolar Pneumonia Suggest Frequent Viral-Bacterial Coinfections.

The World Health Organization Pneumonia Expert Group (WHO-PEG) defined a standardized radiologic endpoint for childhood community-acquired alveolar pneumonia (RD-CAAP), as the most likely to be pneumococcal, not ruling out other bacteria or coinfecting viruses. We aimed to determine the characteristics associated with hospitalization among children <5 years old presenting to the pediatric emergency room (PER) with RD-CAAP. This study was a part of an ongoing prospective population-based surveillance on hospital visits for RD-CAAP. RD-CAAP was determined according to the WHO-PEG. The study was conducted in the prepneumococcal conjugate vaccine era (2004-2008). Of 24,432 episodes with chest radiographs, 3871)15.8%) were RD-CAAP: 2319 required hospitalization and 1552 were discharged (outpatients). Compared with outpatients, hospitalized children had lower temperature, peripheral white cell and absolute neutrophil counts and C reactive protein serum levels, but higher rates of hypoxemia, rhinorrhea, cough and respiratory virus detection. PER visits during the respiratory virus season presented a 1.83 times higher risk of hospitalization than visits during nonrespiratory season. Although RD-CAAP is most often a bacterial infection, the unique characteristics of those visiting the PER and subsequently hospitalized suggest a frequent involvement of respiratory viruses, potentially as viral-bacterial coinfections, compared with outpatients.

Pneumococcal pneumonia and carriage in Africa before and after introduction of pneumococcal conjugate vaccines, 2000–2019: protocol for systematic review

IntroductionAfrica harbours a high burden of pneumococcal disease, with associated high mortality rates. Despite 34 countries introducing the pneumococcal conjugate vaccine, which reduces the risk of pneumococcal carriage (a prerequisite...

Epidemiology of pneumonia in the pre-pneumococcal conjugate vaccine era in children 2-59 months of age, in Ulaanbaatar, Mongolia, 2015-2016.

BackgroundRespiratory diseases, including pneumonia, are the second largest cause of under-five mortality in Mongolia and the most common cause of childhood hospitalization. However information regarding the contribution of Streptococcus pneumoniae to pneumonia causation in Mongolia is limited. We aimed to describe the epidemiology of hospitalized children aged 2–59 months with pneumonia, enrolled into a surveillance program in the period prior to pneumococcal conjugate vaccine (PCV) introduction, in Mongolia.MethodsAn expanded pneumonia surveillance program enrolled children, who met the surveillance case definition, at participating hospitals, between April 2015 and May 2016. Cumulative incidence rates were calculated by district for all pneumonia endpoints using district specific denominators from the Mongolian Health Department census for 2016. Socio-economic and disease-associated factors were compared between districts using chi-squared tests.ResultsA total of 4318 eligible children with pneumonia were enrolled over the 14 month period. Overall the incidence for all-cause pneumonia in children aged 12–59 months was 31.8 per 1000 population; children aged 2–11 months had an almost four-fold higher incidence than children aged 12–59 months.Differences were found between districts with regards to housing type, fuel used for cooking, hospital admission practices and the proportions of severe and primary endpoint pneumonia.DiscussionThis study shows a high burden of pneumonia in children aged 2–59 months in Mongolia prior to PCV introduction. Rates differed somewhat by district and age group and were influenced by a number of socio-economic factors. It will be important to consider these differences and risk factors when assessing the impact of PCV introduction.

Febrile seizures with leukocytosis as a predictor for occult bacteremia.

Febrile children 3-36 months old, who had a body temperature >39°C and white blood cell (WBC) count >15000/mm3 were known to be at risk for occult pneumococcal bacteremia (OPB) in the pre-pneumococcal conjugate vaccine (PCV) era. The positive predictive value of these criteria, however, decreased dramatically after the introduction of PCV, indicating a need for alternative criteria. A high rate of febrile seizures has been noted in children with OPB, suggesting that screening may still be practical in this population. We performed a retrospective analysis to evaluate factors that predict OPB in patients visiting the emergency department (ED) with febrile seizures. Children 3-36 months old who visited the ED for febrile seizures and had blood cultures taken were included. Patients with underlying diseases were excluded from analysis. We performed statistical analyses comparing patient demographics according to the presence or absence of OPB. One thousand and eighty-two patients visited the ED with febrile seizure, and blood cultures were taken in 397, of whom 87% had received more than three doses of PCV. Of the nine patients with OPB, eight (89%) met the risk criteria. In contrast, only 12% (48/388) of those without OPB met the criteria. In this population, those who fulfilled the risk criteria were more likely to have OPB than those who did not (14.3% vs 0.3%; likelihood ratio, 7.17). High WBC count and fever may effectively predict OPB in pediatric patients with febrile seizure in the post-PCV era.

Changes in Serotype of Streptococcus pneumoniae After the Introduction of the 13-Valent Pneumococcal Vaccine in a Homogenous Population on Jeju Island.

We compared the serotypes of Streptococcus pneumoniae between the pre-pneumococcal conjugate vaccine (PCV)13 era and post-PCV13 era among homogenous inhabitants of an isolated South Korean island. A total of 325 S. pneumoniae strains were isolated. In the pre-PCV13 era, 19A/F, 15A/F, 19B, and 23A serotypes were identified. In the post-PCV13 era, 15 serotypes were identified. The 19F and 23A serotypes showed the highest prevalence in the pre- and post-PCV13 era, respectively. After PCV13 introduction, the PCV 13 serotype coverage rate was decreased (80.0% and 30.5% in the pre- and post-PCV13 eras, respectively), while the proportion of non-PCV 13 serotypes increased.

Invasive Pneumococcal Disease Caused by Non-Vaccine Type Multidrug-Resistant Streptococcus pneumoniae Transmitted by Close Contact in a Healthy Adult.

The incidence of vaccine-type Streptococcus pneumoniae carriage and disease have declined in vaccinated children as well as in unvaccinated children and adults. However, diseases caused by non-vaccine type (NVT) S. pneumoniae are increasing. In this study, we report an invasive pneumococcal disease (IPD) caused by NVT multidrug-resistant (MDR) S. pneumoniae transmitted from a vaccinated infant to an unvaccinated healthy woman, and the clinical characteristics of this serotype. A 29-year-old previously healthy woman visited our hospital with fever and headache. She had been breastfeeding her baby for 8 months. She was diagnosed with brain abscess and sinusitis caused by S. pneumoniae. Although the patient had no previous exposure to antibiotics, antibiotic susceptibility test identified the pathogen as MDR. The patient's family members were examined using nasopharyngeal swabs for bacterial culture. The serotype of S. pneumoniae identified from the blood, abscess, and sputum of the patient was 15B/C. After investing the patient's family members, we found that the serotype from nasopharyngeal specimen of her baby was the same. We described an invasive MDR pneumococcal disease in an immunocompetent young adult in the community. IPD likely spread to the patient by close contact with her baby, who harbored S. pneumoniae of NVT. The spread of NVT S. pneumoniae in the post-vaccine era has increased in the community, and resistance pattern for S. pneumoniae of 15B/C changed compared to the pre-pneumococcal conjugate vaccine era. The spread of MDR pathogens causing IPD among family members should be monitored.

Clinical and microbiological characteristics of unusual manifestations of invasive pneumococcal disease

IntroductionInvasive pneumococcal disease (IPD) typically presents as bacterial pneumonia, meningitis or primary bacteraemia. However, Streptococcus pneumoniae can produce infection at any level of the body (endocarditis, arthritis, spontaneous bacterial peritonitis, etc.), which is also known as unusual IPD (uIPD). There are very limited data available about the clinical and microbiological profile of these uncommon manifestations of pneumococcal disease. Our aim was to analyse clinical forms, microbiological profile, epidemiology and prognosis of a cohort of patients with unusual invasive pneumococcal disease (uIPD). MethodsWe present a retrospective study of 389 patients (all adult and paediatric patients diagnosed during the period) diagnosed with IPD at our hospital (Complejo Hospitalario Universitario de Vigo) between 1992 and 2014. We performed an analysis of clinical, microbiological and demographical characteristics of patients comparing the pre-pneumococcal conjugate vaccine (PCV) period with the post-vaccination phase. IPD and uIPD were defined as follows; IPD: infection confirmed by the isolation of S. pneumoniae from a normally sterile site, which classically presented as bacterial pneumonia, meningitis or primary bacteraemia; uIPD: any case of IPD excluding pneumonia, meningitis, otitis media, rhinosinusitis or primary bacteraemia. ResultsA total of 22 patients (6%) met the criteria of uIPD. A Charlson index >2 was more prevalent in uIPD patients than IPD patients (45% vs 24%; p=0.08). The most common clinical presentation of uIPD was osteoarticular infection (8 patients, 36%), followed by gastrointestinal disease (4 patients, 18%). Infection with serotypes included in PCV-13 was significantly higher in IPD patients (65%) than in patients with uIPD, 35% (p=0.018). Conversely, infection with multidrug-resistant strains was higher among patient with uIPD (27% vs 9%; p=0.014). The all-cause mortality rate was 15%, 13% in the IPD group and 32% among patients with uIPD (p=0.07). According to the multivariate analysis, a Charlson Index >2 (OR 5.1, 95% CI, 1.8•14.0) and a Pitt Score >2 (OR 1.4, 95% CI, 1.2•1.9) were independent predictors of mortality. ConclusionuIPD is a rare entity that affects patients with more comorbidities than typical IPD and it is usually caused by non-vaccine serotypes with greater antimicrobial resistance.

Clinical and microbiological characteristics of unusual manifestations of invasive pneumococcal disease

IntroductionInvasive pneumococcal disease (IPD) typically presents as bacterial pneumonia, meningitis or primary bacteraemia. However, Streptococcus pneumoniae can produce infection at any level of the body (endocarditis, arthritis, spontaneous bacterial peritonitis, etc.), which is also known as unusual IPD (uIPD). There are very limited data available about the clinical and microbiological profile of these uncommon manifestations of pneumococcal disease. Our aim was to analyse clinical forms, microbiological profile, epidemiology and prognosis of a cohort of patients with unusual invasive pneumococcal disease (uIPD). MethodsWe present a retrospective study of 389 patients (all adult and paediatric patients diagnosed during the period) diagnosed with IPD at our hospital (Complejo Hospitalario Universitario de Vigo) between 1992 and 2014. We performed an analysis of clinical, microbiological and demographical characteristics of patients comparing the pre-pneumococcal conjugate vaccine (PCV) period with the post-vaccination phase. IPD and uIPD were defined as follows; IPD: infection confirmed by the isolation of S. pneumoniae from a normally sterile site, which classically presented as bacterial pneumonia, meningitis or primary bacteraemia; uIPD: any case of IPD excluding pneumonia, meningitis, otitis media, rhinosinusitis or primary bacteraemia. ResultsA total of 22 patients (6%) met the criteria of uIPD. A Charlson index >2 was more prevalent in uIPD patients than IPD patients (45% vs 24%; p=0.08). The most common clinical presentation of uIPD was osteoarticular infection (8 patients, 36%), followed by gastrointestinal disease (4 patients, 18%). Infection with serotypes included in PCV-13 was significantly higher in IPD patients (65%) than in patients with uIPD, 35% (p=0.018). Conversely, infection with multidrug-resistant strains was higher among patient with uIPD (27% vs 9%; p=0.014). The all-cause mortality rate was 15%, 13% in the IPD group and 32% among patients with uIPD (p=0.07). According to the multivariate analysis, a Charlson Index >2 (OR 5.1, 95% CI, 1.8–14.0) and a Pitt Score >2 (OR 1.4, 95% CI, 1.2–1.9) were independent predictors of mortality. ConclusionuIPD is a rare entity that affects patients with more comorbidities than typical IPD and it is usually caused by non-vaccine serotypes with greater antimicrobial resistance.

Global Burden of Neonatal Invasive Pneumococcal Disease: A Systematic Review and Meta-analysis.

This study aimed to estimate the global burden of invasive pneumococcal disease (IPD) incidence among neonates during the pre-pneumococcal conjugate vaccine era. A systematic search of published and unpublished data was undertaken. Bias assessment and qualitative synthesis of the included studies were carried out. Random effects models using the method of DerSimonian and Laird were constructed. Subgroup analyses, sensitivity analyses and meta-influence analysis were undertaken. Sources of heterogeneity were investigated. From 26 neonatal IPD data points in the pre-pneumococcal conjugate vaccine era, the overall pooled neonatal IPD incidence, in the general population, combining all 3 United Nations (UN) country strata was estimated to be 36.0 per 100,000 live births [95% confidence interval (CI): 20.0-64.7 per 100,000]. The pooled neonatal IPD incidence in the general population in the less-developed UN country strata was estimated to be 16.0 per 100,000 live births (95% CI: 3.9-65.6 per 100,000) and in the more-developed stratum was 41.1 per 100,000 live births (95% CI: 29.1-58.1 per 100,000). This counter-intuitive finding is likely to have been affected by data quantity and confounding by time. A pooled estimate for the least-developed stratum was not computable as there was only 1 study in this stratum-a study from The Gambia with an unweighted IPD incidence of 369.5 per 100,000 (95% CI: 119.2-1138.5 per 100,000). Pneumococcus was a recognized pathogen among neonates in all development regions of the world. The burden of neonatal IPD, particularly in the least-developed UN country stratum, requires substantial further evaluation.

Streptococcus pneumoniae Serotypes and Mortality in Adults and Adolescents in South Africa: Analysis of National Surveillance Data, 2003 - 2008.

BackgroundAn association between pneumococcal serotypes and mortality has been suggested. We aimed to investigate this among individuals aged ≥15 years with invasive pneumococcal disease (IPD) in South Africa.MethodsIPD cases were identified through national laboratory-based surveillance at 25 sites, pre-pneumococcal conjugate vaccine (PCV) introduction, from 2003–2008. We assessed the association between the 20 commonest serotypes and in-hospital mortality using logistic regression with serotype 4 (the third commonest serotype with intermediate case-fatality ratio (CFR)) as referent.ResultsAmong 3953 IPD cases, CFR was 55% (641/1166) for meningitis and 23% (576/2484) for bacteremia (p<0.001). Serotype 19F had the highest CFR (48%, 100/207), followed by serotype 23F (39%, 99/252) and serotype 1 (38%, 246/651). On multivariable analysis, factors independently associated with mortality included serotype 1 (OR 1.9, 95%CI 1.1–3.5) and 19F (OR 2.9, 95%CI 1.4–6.1) vs. serotype 4; increasing age (25–44 years, OR 1.8, 95%CI 1.0–3.0; 45–64 years, OR 3.6, 95%CI 2.0–6.4; ≥65 years, OR 5.2, 95%CI 1.9–14.1; vs. 15–24 years); meningitis (OR 4.1, 95%CI 3.0–5.6) vs. bacteremic pneumonia; and HIV infection (OR1.7, 95%CI 1.0–2.8). On stratified multivariate analysis, serotype 19F was associated with increased mortality amongst bacteremic pneumococcal pneumonia cases, while no serotype was associated with increased mortality in meningitis cases.ConclusionMortality was increased in HIV-infected individuals, which may be reduced by increased antiretroviral therapy availability. Serotypes associated with increased mortality are included in the 10-and-13-valent PCV and may become less common in adults due to indirect effects following routine infant immunization.

Challenges in the Surveillance of Invasive Pneumococcal Disease in the Postvaccination Era.

Worldwide, meningitis and pneumonia are the leading cause of morbidity and mortality in children. Invasive pneumococcal disease (IPD) is the leading cause of vaccinepreventable deaths, accounting for 11% of deaths in children <5 years globally in the pre-pneumococcal conjugate vaccine (PCV) era [1], and it causes significant disease burden in Latin America (LA) and the Caribbean. According to data published by the Pan American Health Organization (PAHO) in July 2014, 25 countries from LA and the Caribbean have introduced PCVs in their immunization schedules. Bolivia is the latest country that has introduced the 13-PCV in their national immunization program. The First Latin American Meeting of Pneumococcus: Epidemiology and Impact of Pneumococcal Conjugate Vaccines was held in San Jose, Costa Rica in August 2014 given the importance of analyzing the data of the post-PCVs era and its impact since their introduction in different countries.

Seasonality of Both Bacteremic and Nonbacteremic Pneumonia Coincides With Viral Lower Respiratory Tract Infections in Early Childhood, in Contrast to Nonpneumonia Invasive Pneumococcal Disease, in the Pre-Pneumococcal Conjugate Vaccine Era

We assessed the seasonality of viral lower respiratory tract infections (V-LRI), bacteremic pneumonia, nonbacteremic pneumonia and nonpneumonia invasive pneumococcal diseases (IPD) in the pre-PCV era. Both bacteremic and nonbacteremic pneumonia seasonality peaked in winter, coinciding with V-LRI seasonality, whereas non-pneumonia IPD peaked in autumn before V-LRI increase, suggesting different pathogenesis.

Global Pneumococcal Disease and Policies for Control

Oral Poster AbstractsISPPD-0508 Global Pneumococcal Disease and Policies for Control: GLOBAL SEROTYPE DISTRIBUTION OF INVASIVE PNEUMOCOCCAL DISEASE (IPD) IN OLDER CHILDREN AND ADULTS: THE AGEDD STUDYM. Deloria Knoll1, B.A. Nonyane2, C. Garcia1, O.S. Levine3, K.L. O’Brien1, H.L. Johnson41International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA; 2International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA; 3Global Development Program, Bill & Melinda Gates Foundation (formerly of JHSPH), Seattle WA, USA; 4Monitoring & Evaluation Policy & Performance, GAVI Alliance (formerly of JHSPH), Geneva, SwitzerlandBackground and Aims: Global serotype distribution of IPD in children ≥5 years old and adults pre-pneumococcal conjugate vaccine (PCV) introduction has not been described. We aimed to estimate the proportion due to top serotypes by geographic region.Methods: A systematic literature review identified studies reporting ≥20 IPD cases with serotype/serogroup information. We estimated the proportion of IPD due to 20 serotypes: PCV13-type, 22F, 32F, and any others in the top 13 of each geographic region (8, 9N, 10A, 12F, 16F, 20D). All other serotypes were grouped. Random-effects meta-analysis was used to estimate the average serotype proportion, normalizing to 100 percent.Results: Analyses included 72,954 isolates (>3500 in each region) from children ≥5 years and adults from 77 studies in 53 countries. 70% of disease was accounted for by 9 serotypes in Africa, 12 in North America, 12 in Europe, 13 in Oceania, 14 in Latin America and Caribbean and 16 in Asia. Serotype 1 or 14 was the most common in all regions. Six serotypes (3, 6B, 7F, 14, 19F, 23F) were among the top 13 in all regions. Eleven serotypes (1, 3, 4, 5, 6B, 8, 9V, 14, 19A, 19F, 23F) covered the top 5 in all regions. Vaccine serotypes accounted for >50% of IPD: regional PCV10 plus 6A coverage range=52–62%, PCV13=60–75%, PCV15=64–77%, and 19/23 serotypes in polysaccharide vaccine (PPV23)=72–87%.Conclusion: A limited set of serotypes are common in older children and adults in all regions. Serotypes in existing vaccines included >50% of IPD. PCV13 and PPV23 add approximately 10% and 24%, respectively.No conflict of interestISPPD-0273 Global Pneumococcal Disease and Policies for Control: MENINGOENCEPHALITIS: STREPTOCOCCUS PNEUMONIAE IS AMONG THE MAJOR CAUSES IN ADULTS IN RURAL KENYAA. Amulele1, C. Harris1, M. Ooko1, A. Mwanzu1, R. Njeru1, A. Etyang1, J.A.G. Scott1, J.A.G. Scott2, S.C. Morpeth1, S.C. Morpeth31Epidemiology and Demographic, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya; 2Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom; 3Nuffield Department of Clinical Medicine John Radcliffe Hospital, University of Oxford, London, United KingdomBackground and Aims: We aimed to identify the aetiology of meningoencephalitis in adult patients at Kilifi District Hospital (KDH) and to describe their clinical presentations and outcomes.Methods: Adult patients admitted to KDH, January 2007–October 2012, with any two of: temperature >37.5°C, meningism, altered mental status; were suspected meningoencephalitis cases, eligible for a lumbar puncture (LP). Patients with cerebrospinal fluid (CSF) collected and stored during this period were included. Real-time multiplex PCR (Fast-Track Diagnostics, Luxembourg) targeting 21 pathogens and a cryptococcal antigen lateral-flow assay (Immuno-Mycologics, USA) were performed retrospectively and analyzed with microscopy, culture, antigen tests and clinical data from admission.Results: Adults admitted to the wards were 18,527; 665 (3.6%) met the LP criteria, performed in 554 (83%) patients. CSF samples for 357 (64%) clinical episodes were sufficient for storage. Of 268 (75%) episodes tested, 11 from 2007 and 257 from 2010 to 2012, 161 (60%) were abnormal and consistent with suspected meningoencephalitis. A pathogen was identified in 50 (31%) abnormal episodes; 22/159 (14%) with Cryptococcus neoformans, 11/160 (7%) with Streptococcus pneumoniae. HIV prevalence recorded in cryptococcal or pneumococcal meningitis patients was 20/21 (95%) and 5/10 (50%) respectively and overall at 71% (104/147). Death in hospital occurred in 76/159 (48%) episodes, 7 (64%) with pneumococcal meningitis, 10 (45%) with cryptococcal meningitis.Conclusion: S. pneumoniae is a major cause of morbidity and mortality in adult meningoencephalitis in Kenya, after C. neoformans. Pneumococcal conjugate vaccine was introduced in Kenya in 2011 and CSF PCR may enhance the evaluation of impact.No conflict of interestISPPD-0505 Global Pneumococcal Disease and Policies for Control: IMPACT OF THIRTEEN-VALENT PNEUMOCOCCAL CONJUGATE VACCINE ON PNEUMOCOCCAL CARRIAGE IN DIFFERENT COUNTRIES — MATHEMATICAL MODELLING STUDYY. H. Choi1, A. Melegaro2, A. Hoek3, G. Mackenzie4, N. Gay51Immunisation Hepatitis and Blood Safety Department, Public Health England — Colindale, London, United Kingdom; 2DONDENA Centre for Research on Social Dynamics, Bocconi University, Milan, Italy; 3Immunisation Hepatitis and Blood Safety Department, Public Health England, London, United Kingdom; 4Medical Research Council (UK), Medical Research Council (UK), Fajara and Basse stations, Gambia; 5Hungerford, Fu Consulting, Berkshire, United KingdomBackground and Aims: Many developed countries have introduced various pneumococcal conjugate vaccines (PCV) and almost eliminated PCV serotypes from their populations. Many other countries, inspired by this impact, are now considering introduction of PCV into their National Immunisation Programmes. As the carriage prevalence and serotype distributions can vary widely between countries, a different impact of the PCV programme is possible. PCV13’s protection against development of invasive disease is high, but protection against carriage is weaker; the degree of protection against acquisition of carriage is little more than 50%, and the duration of this protection is thought to be short. This raises the question of whether such a vaccine will be able to eliminate PCV subtypes from high prevalence populations. This question is addressed using mathematical models.Materials and Methods: A simple age-structured compartmental model was developed to describe the transmission dynamics of pneumococci in the Gambia, and in England & Wales (E&W). Local pre-PCV carriage data were used to estimate transmission parameters in the model. A simulation model assessed the long-term impact of the PCV13 programmes in these two countries.Results: Simulation results suggest that all E&W vaccination scenarios have the potential to eliminate PCV13 serotypes from circulation. Conversely, model simulations for the Gambia scenarios produced a reduction in the level of PCV13 serotype carriage prevalence but failed to eliminate PCV13 serotypes.Conclusion: In developed countries, where carriage is concentrated among young children, PCV13, despite its limited protection against carriage, can eliminate PCV13 serotypes from the population. However, in developing countries with a high carriage prevalence among adults, PCV13 may not be able to eliminate PCV13 serotypes.No conflict of interestISPPD-0245 Global Pneumococcal Disease and Policies for Control: UNDERSTANDING THE IMPACT OF PNEUMOCOCCAL CONJUGATE VACCINE IN INDIA: A SYSTEMATIC COMPARISON OF IMPACT ESTIMATES FOR PCV, HIB AND ROTAVIRUS VACCINESK. Hayford1, B. Wahl2, R. Kumar3, N. Thacker4, A. Sutherland2, L. Privor-Dumm2, M. Santosham2, K. O’Brien21Department of Medicine, University Health Network, Toronto, Canada; 2International Health, Johns Hopkins School of Public Health, Baltimore, USA; 3PGIMER School of Public Health, Chandigarh, India; 4Child Health Foundation, Gandhidham, IndiaBackground & Aims: The Indian National Technical Advisory Group on Immunization (NTAGI) recommended pneumococcal conjugate vaccine (PCV) introduction in >1 state in 2008, but the recommendation has not yet been implemented. Some stakeholders argued there were insufficient health and economic impact data to support use of PCV in India. Multiple estimates are now available, creating a challenge for advocacy and communication efforts.Methods: We conducted a review of all published and unpublished national-level modeled estimates of pneumococcus, Haemophilus influenzae type b (Hib), and rotavirus morbidity and mortality, and health and economic impact estimates of these preventive vaccines.Results: Four national pneumococcal mortality estimates are available-two published estimates for year 2000 (all syndromes) and 2010–2011 (pneumococcal pneumonia only) and two unpublished estimates (2005, 2008—all syndrome). 142,361 pneumococcal deaths were estimated in 2000; 136,100 in 2005; and 79,450 in 2008; but models and assumptions are not consistent across estimates. State-level pneumococcal mortality estimates(year 2005) are available but not yet published. National health or economic impact estimates for PCV in India exist but are unpublished. Impact estimates for Hib (n = 1) and rotavirus vaccines (n = 7) are available but assumptions, disease burden and economic inputs are not consistent with PCV impact models.Conclusion: Pneumococcal disease burden estimates in India are available for various years; inferences about changes in disease burden over time are not recommended because modeling strategies are not consistent. Generating robust health and economic impact estimates for PCV -at the state and national level using methods that are comparable to other vaccine impact estimates- will support evidence-based decisions for PCV introduction in India.No conflict of interestISPPD-0486 Global Pneumococcal Disease and Policies for Control: METHODOLOGICAL ISSUES IN THE ANALYSIS OF ‘BEFORE AND AFTER’ VACCINE STUDIESD. Jeffries1, P. Hill2, S. Howie3, E.K. Mulholland4, B. Greenwood5, G. Mackenzie31Statistics, Medical Research Council The Gambia Unit, Fajara, Gambia; 2Centre for International Health, School of Medicine University of Otago Dunedin NZ, Dunedin, New Zealand; 3Child Survival Theme, Medical Research Council The Gambia Unit, Fajara, Gambia; 4Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom; 5Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United KingdomBackground and Aims: Evaluation of vaccine impact using ‘before and after’ data is complicated by temporal changes in factors which may confound or bias results. We addressed these issues in a study of the impact of pneumococcal conjugate vaccine in The Gambia.Methods: We analysed incidence of primary end-points in pre- and post-intervention periods and performed a cohort analysis. For the pre- and post-analysis, we defined the start of the intervention period as the date when coverage of ≥2 doses across an age range approached its maximum. Individuals may contribute time in both ‘before’ and ‘after’ periods (accounted for by a random effect for subject) to reduce loss of information. We defined potential confounders (e.g. season, malaria) and adjusted for changes in the comparison periods. We identified potential biases, such as changes in case ascertainment or the prevalence of serotypes known to vary markedly over time, and included these variables in stratified and multivariable modelling. End-points unrelated to vaccination (e.g. Gram-negative bacteraemia) were used to indicate potential confounding or bias. We estimated variance using robust methods. Children eligible for vaccination were included in the cohort analysis which may be interpreted as vaccine effectiveness at the individual level. To facilitate control of confounding we used a time-to-event approach specifying vaccination status and age as time-varying covariates. Results are presented in plenary session 6.Conclusion: Analytic techniques are available to improve the evaluation of new vaccines using ‘before and after’ data while taking into account potential confounding and bias.No conflict of interestISPPD-0492 Global Pneumococcal Disease and Policies for Control: INVASIVE SEROTYPES AND PNEUMOCOCCAL MENINGITIS FATALITY IN BURKINA FASO AND TOGO, 2002–2013B.D. Gessner1, S. Yaro2, T.A. Tamekloe3, B. Nacro4, K. Agbenoko5, S. Kroman6, O. Sanou6, J.C. Moisi7, J.E. Mueller8, B.M. Njanpop-Lafourcade81NA, Agence de Medecine Preventive, Paris, France; 2NA, Centre Muraz, Bobo-Dioulasso, Burkina Faso; 3NA, Ministère de la Santé, Lome, Togo 4NA, Centre Hospitalier Universitaire Sourou Sanou, Bobo-Dioulasso, Burkina Faso; 5NA, Centre Hospitalier Regional des Savanes, Dapaong, Togo; 6NA, Agence de Medicine Preventive, Ouagadougou, Burkina Faso; 7NA, Agence de Medicine Preventive, Ferney-Voltaire, France; 8NA, Agence de Medicine Preventive, Paris, FranceBackground and Aims: Many pneumococcal (Sp) meningitis cases in the African meningitis belt result from the invasive serotype 1, which data from other areas indicate should present with relatively low mortality.Methods: We evaluated all age acute bacterial meningitis mortality data from healthcare structure based surveillance systems in northern Togo and western Burkina Faso. All patients had received care based on standard algorithms. Etiologic determination was performed via culture, antigen detection, or polymerase chain reaction (PCR) while serotype/group was determined by PCR or Quellung.Results: Among 4838 patients, the case fatality ratio (CFR) was 34% (275/808) for Sp, and 9% (56/639), 11% (26/229), and 15% (17/111) for serogroups A, W135, and X meningococcus, respectively. Sp CFR varied only modestly by study year (23% [2005] to 46% [2010]) and age group (31% [5–14 years] to 43% [50+ years]) with no particular trend; 56% of Sp deaths occurred from age 5–49 years. Of 355 (43%) evaluated Sp cases, 51% were serotype 1 and 66% were invasive (serotype/groups 1, 4, 5, 7, 14, 18). CFR was 42% for serotype 1 versus other serotypes and for invasive versus non-invasive serotypes. Serotype 1 and invasive serotypes were not associated with lower CFR when stratified by country, age group, or study year. Antibiotic resistance did not predict death.Conclusion: In the African meningitis belt Sp meningitis mortality is higher than other etiologies, affects all age groups, shows no evidence of decreasing, and is not lower for serotype 1 or the broader category of invasive serotypes.Conflict of interestISPPD-0147 Global Pneumococcal Disease and Policies for Control: RELATIVE RATES OF PNEUMOCOCCAL DISEASE ARE DISPROPORTIONATELY HIGH IN ADULTS WITH MULTIPLE CHRONIC MEDICAL CONDITIONSS.I. Pelton1, D. Weycker2, R.A. Farkouh3, K.M. Shea1, J. Edelsberg2, D.R. Strutton31Schools of Medicine and Public Health, Boston University, Boston, USA; 2Outcomes Research, Policy Analysis Inc., Boston, USA; 3Vaccines, Pfizer, Collegeville, USABackground: The high risk of pneumococcal infection among adults with immunocompromising conditions is well recognized; however, the risk among immunocompetent adults with chronic medical conditions, especially those with multiple conditions, is less well established.Methods: A retrospective cohort design using US healthcare claims data (2007–2010) from >35M persons annually was employed. Study population included persons aged ≥18 years, and was stratified by age and risk profile (high-risk [immunocompromised], at-risk [immunocompetent with ≥1 chronic condition], healthy); at-risk individuals were further stratified by number of conditions. At-risk and high-risk conditions, and episodes of pneumococcal disease (PD)—invasive (IPD), pneumococcal pneumonia (PP), all-cause pneumonia (PNE)—were identified via diagnosis, procedure, and drug codes.Results: Persons with ≥2 at-risk conditions accounted for 9–32% of all at-risk adults, depending on age. PD rates increased markedly with number of conditions, and for those with ≥2 conditions, were similar to those in the high-risk group (Table). Among adults 18–34 years, 66–71% of PD occurred in healthy individuals and 4–7% among those with ≥2 at-risk conditions; among adults ≥65 years, corresponding figures were 20–21% and 26–29%. Conclusion: Notwithstanding widespread childhood pneumococcal vaccination and an overall decline in PD among adults, disease risk remains disproportionately high in those with at-risk and high-risk conditions. PD rates are notably high among adults with multiple at-risk conditions; comparable to those among adults with high-risk conditions.Conflict of interestISPPD-0370 Global Pneumococcal Disease and Policies for Control: PNEUMOCOCCAL POLYSACCHARIDE VACCINE AT 9 MONTHS OF AGE IS NOT ASSOCIATED WITH IMPAIRED B-CELL MEMORY OR HYPO-RESPONSIVENESS IN CHILDREN IN PNGP. Richmond1, W.S. Pomat2, A. Fuery1, J.P. Francis2, C. Opa2, P. Siba3, G. Saleu2, D. Anderson4, P. Jacoby4, D. Lehmann4, P. PCV Study Team21Paediatrics and Child health, University of Western Australia, Perth, Australia; 2Infection and Immunity, Papua New Guinea Institute of Medical research, Perth, Australia; 3Director, Papua New Guinea Institute of Medical research, Perth, Australia; 4Telethon Institute for Child health Research, University of Western Australia, Perth, AustraliaIntroduction: 23-valent pneumococcal polysaccharide vaccine (PPV) following pneumococcal conjugate vaccines (PCV) should increase protection however concerns exist regarding hypo-responsiveness and B-cell memory impairment after PPV. We evaluated the persistence of antibody and B-cell memory following PPV at 9 months of age in 3–5 year old children in Papua New Guinea.Methods: 150 children who had received PPV at age 9 mo (after PCV7 at 0–1–2 or 1–2–3 months or no PCV7) and 130 age-matched unvaccinated controls received a 0.1 mL PPV challenge dose at age 3–5 years and blood was collected pre- and 1 month post-challenge. Serotype-specific IgG for serotypes in PCV7 (VT), 2, 5 & 7F was measured by ELISA. B-cell memory for serotypes 1, 2, 7F, 14, 19A, 19F & 23 was measured at age 10 and 18 months (prior-PPV groups) and pre-challenge by polyclonal B-cell stimulation and detection of antibody forming cells on polysaccharide-coated plates by ELISpot.Results: Post-PPV, memory B-cells numbers increased from age 10 months to 3–5 years for 8/9 serotypes (not 23F) and did not differ to PPV naïve controls. Pre-challenge, IgG levels were high, with no significant differences between groups in GMCs or proportions ≥1 µg/mL (range 58–95%). IgG increases after PPV-challenge were modest (1.2 to 2.8-fold) with no significant differences in GMCs, fold-rises or % ≥1 µg/mL between groups. Increased pre-challenge antibody concentrations were associated with a decreased IgG response to challenge.Conclusion: We found no evidence of hypo-responsiveness or impairment of memory B-cells in PNG children at 3–4 years of age after PPV at age 9 months.Conflict of interestISPPD-0496 Global Pneumococcal Disease and Policies for Control: OTITIS MEDIA AND ITS SEQUELAE IN KENYAN SCHOOL CHILDRENE. Simões1, I.M. Macharia2, F. Kiio2, P. Carosone-Link1, S.N. Ndegwa2, J. Ayugi21Dept. of Global Health, University of Colorado at Denver, Denver, USA; 2Dept. of Surgery, University of Nairobi Kenyatta National Hospital, Nairobi, KenyaBackground and Aims: Chronic suppurative otitis media (CSOM), a sequel of acute otitis media (AOM) is a major cause of preventable hearing loss in children in developing countries. In Africa there are few recent studies on the prevalence of AOM and its sequelae. Obtaining representative Kenyan data on the point prevalence of AOM and its sequelae, otitis media with effusion (OME), CSOM and hearing impairment was the goal.Methods: Study subjects were children aged 2 to 15 years enrolled from randomly selected preprimary and primary schools. With parental/guardian consent, subjects had a questionnaire administered, otoscopy and tympanometry done, and audiometry performed on those with ear problems detected on these examinations.Results: Of the 13,109 children examined, 75% were from rural schools. The prevalence’s of CSOM and OME were 15/1000 children and AOM was 7/1000. Apart from retraction of the tympanic membrane (urban 0.3%, rural 0.1%, p < 0.001), there was no statistically significant difference between the prevalence of other middle ear disorders in rural and urban school children. However in rural children, those from the Rift Valley had a significantly higher rate of CSOM 24/1000 than other regions 12/1000; p < 0.0001. The age of onset of ear discharge was before 3.5 years in 50% of children and before 6 years in 75%.Conclusion: Since a significant burden of AOM sequelae occur in Kenyan preschool and school children with the onset mostly, in the first 4 years of life, we question: would pneumococcal vaccines that prevent early recurrent AOM, prevent these nonreversible sequelae?No conflict of interestISPPD-0355 Global Pneumococcal Disease and Policies for Control: EPIDEMIOLOGY OF INVASIVE PNEUMOCOCCAL DISEASE IN HIV EXPOSED-UNINFECTED CHILDREN <1 YEAR OF AGE IN SOUTH AFRICA, 2009 THROUGH 2012C. von Mollendorf1, A. von Gottberg1, S. Meiring2, L. de Gouveia1, V. Quan2, S. Lengana1, K.L. O’ Brien3, K.P. Klugman4, C. Cohen11Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Johannesburg, South Africa; 2Division of Public Health Surveillance and Response, National Institute for Communicable Diseases, Johannesburg, South Africa; 3Center for American Indian Health & International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA; 4Hubert Department of Global Health Rollins School of Public Health and Division of Infectious Diseases, Emory University, Atlanta, USABackground: The prevention of mother-to-child transmission (PMTCT) programme has been rapidly scaled-up in South Africa with a reported decrease in HIV transmission rates from 3.5% (2010) to 2.7% (2011). There are no published data quantifying specific increased risk or mortality of IPD in HIV-exposed uninfected (HEU) children.Methods: We conducted a cohort surveillance study in children <1 year of age with invasive pneumococcal disease (IPD), using data obtained from a national, laboratory-based, surveillance programme. HIV and outcome data were obtained at sentinel sites. Incidences in HIV-infected, HIV-uninfected, HEU and HIV-unexposed uninfected (HUU) children were calculated assuming similar annual HIV prevalence in tested and untested children.Results: We identified 1805 IPD cases in children <1 year of age from 2009 through 2012 from all sites. In children from sentinel sites (n=863), 89% (768/863) had known HIV status. The highest incidence of IPD was in HIV-infected (608/100,000 population) compared with HIV-uninfected children (31/100,000; crude relative risk 19.61 [95% CI 13.67–29.12]). In addition, HEU children had higher incidence of IPD (61/100,000 population) than HUU children (22/100,000; crude relative risk 2.77 [95% CI 1.68–4.74]).Overall case-fatality ratio was high (27%, 234/863), differed between HIV-infected (32%, 75/231) and HIV-uninfected children (24%, 129/537, p=0.008); as well as between HEU (27%, 59/220) and HUU children (21%, 57/266, p=0.08).Discussion: The numbers of HIV-exposed children infected annually continue to drop due to improvements in PMTCT; however we have now shown that these exposed but uninfected children are at increased risk of IPD and mortality compared with HIV-unexposed children.No conflict of interestISPPD-0437 Global Pneumococcal Disease and Policies for Control: SEROTYPE DISTRIBUTION OF STREPTOCOCCUS PNEUMONIAE ASSOCIATED WITH INVASIVE PNEUMOCOCCAL DISEASE IN CHINAM.C. Li1, Z.J. Shao1, Y. Wang2, W.M. Tang3, H.K. Yang41Respiratory infection department, Chinese Center for Disease Control and Prevention(ICDC China CDC), Beijing, China; 2Department of laboratory medicine, Peking Union Medical College Hospital, Beijing, China; 3Medical Affairs, MSD China Holding Co. Ltd, Shanghai, China; 4Global Health Outcomes, Merck, West Point, USABackground and Aims: Invasive pneumococcal disease (IPD) is a serious public health problem in China, yet epidemiology data are limited, especially in adults. The study aimed to examine the serotype distribution of Streptococcus pneumoniae isolated from Chinese patients with IPD.Methods: The multicenter study collected S. pneumoniae positive IPD isolates from normally sterile sites in both pediatric (<18 years) and adult (≥18 years) patients in China between 2009 and 2013. Serotypes were analyzed by Chinese Center for Disease Control and Prevention using Capsule-quellung test.Results: A total of 110 isolates from 60 pediatric and 50 adult IPD cases were collected from 16 hospitals in 13 provinces in China. Overall, the most common serotypes in all ages were 19A, 19F, 23F, 3 and 14. The most frequent serotypes were 19A, 19F, 23F, 1, 5, 14, 6B and 6C in pediatric patients and 3, 19F, 19A, 23F, 14, 20 and 6A in adults. Interestingly, serotype 19A appeared significantly more frequent in infants (<2 years) than other age groups, whereas serotype 3 was the most common type in the elderly (>65 years). The common serotypes for main IPD diagnoses (invasive pneumonia, meningitis and sepsis) were 19A, 19F and 23F in invasive pneumonia and meningitis, and 19F, 19A, 5, 1 and 23F in sepsis.Conclusion: Serotypes 19A and 3 were the most prominent serotypes in pediatric and adult patients with IPD, respectively. Findings demonstrate the different serotype distribution among various age groups in Chinese population with IPD.Conflict of interest

Pneumococcal meningitis: clinical outcomes in a pre-vaccine era at a Dublin paediatric hospital, 1999–2007

To document the long-term outcomes of pneumococcal meningitis in children presenting to a Dublin paediatric hospital in the pre-pneumococcal conjugate vaccine (PCV7) era (1998-2007). Subjects with pneumococcal meningitis were identified at The Children's University Hospital, Dublin through the hospital surveillance system and laboratory archives. 44 children were identified with S. pneumoniae meningitis. Mean age of presentation was 23.45 months (2 days to 13 years) and 28 (65%) cases were less than 12 months old. Eight (18.6%) children died. 55% of cases were left with significant deficits. Of the survivors, 7 (20%) had moderate to severe neurological sequelae. Pneumococcal meningitis is a devastating childhood disease with significant mortality and morbidity, especially in those less than 2 years of age. These data provide a baseline against which the impact of PCV7 on pneumococcal meningitis can be measured.

Pneumonia After Implementation of the Pneumococcal Conjugate Vaccine Program in the Province of Quebec, Canada

In Canada, a pneumococcal conjugate vaccine was licensed in 2001, and in the province of Quebec, a publicly-funded program was implemented for high-risk children in 2002, using a 4-dose schedule, and for all children in 2004, using a 3-dose schedule. To describe the epidemiology of hospitalized pneumonia in the population aged <5 years. Hospital discharge records with a main diagnosis of pneumonia, pleurisy, or empyema were analyzed regarding monthly frequencies by diagnostic categories, duration of stay, proportion of cases admitted to the intensive care unit, and case fatality. Lobar pneumonia represented 32% of 25,319 all-cause pneumonia admissions during the period April 1997 to March 2006. Beginning in the spring of 2004, there was a marked decrease in the frequency of lobar pneumonia, whereas unspecified pneumonia tended to increase to a lesser extent. Compared with the pre-pneumococcal conjugate vaccine period, admissions for all-causes pneumonia decreased by 13% after program implementation and there was no increase in empyema cases. Results are reassuring as to the effectiveness of the pneumococcal vaccination program in Quebec.

The Impact of Conjugate Pneumococcal Vaccination on Routine Childhood Vaccination and Primary Care Use in 2 Counties

Pneumococcal conjugate vaccine immunization recommendations were rapidly implemented by primary care providers. Before the recommendations, concern was expressed that adding pneumococcal conjugate vaccine might result in delays in other vaccinations or preventive services. The study objectives were to measure whether incorporation of pneumococcal conjugate vaccine by primary care providers delayed other vaccinations or added primary health care visits. In 2 counties surrounding Rochester and Nashville, we reviewed a representative sample of primary care charts for children born before and after licensure of pneumococcal conjugate vaccine. Receipt of vaccinations and health care visits were compared for the 2 age-matched cohorts. We reviewed 1459 records from Rochester and 1857 records from Nashville. The pre-pneumococcal conjugate vaccine and post-pneumococcal conjugate vaccine cohorts had similar demographic characteristics. The median age for receipt of any vaccination was not older for the postvaccine cohort than for the prevaccine cohort in either community. The percentage of children up-to-date for vaccinations by 18 months for postvaccine versus prevaccine cohorts was similar in Rochester (72% in each cohort) and in Nashville (58% postvaccine and 65% prevaccine). The number of well-child care visits or other health care visits during the first 18 months of life was not statistically different between the 2 cohorts. Implementation of pneumococcal conjugate vaccine was not associated with delays in other childhood vaccinations or more primary care visits.