Pneumococcal Disease In Children Research Articles

Development of Nanogel-based Nasal Vaccine against Pneumonia

Abstract Streptococcus pneumoniae (S. pneumoniae) cause pneumococcal disease in children and adults all over the world. Although there are vaccines comprising several pneumococcal polysaccharides in clinical use, they cannot cover the broad protections. Recently we established the cationic nanogel-based nasal vaccine against Pneumonia using a recombinant protein of pneumococcal surface protein A (PspA). We have designed three PspA chimeric antigens for trivalent vaccine and combined them with a cationic nanogel, a novel drug delivery system which adhere to the epithelial layer of the nasal cavity after nasal immunization and elicit the effective immunity by sustained antigen release. Indeed, the PspA nanogel vaccine induced not only the antigen-specific IgG in the body but also the antigen-specific secretory IgA (SIgA) at the mucosal surfaces such as nasal cavity where the entrance of pathogens. Both induced antigen-specific IgG and SIgA could bind to various serotypes of S. pneumoniae, indicating that these antibodies have neutralizing activity against broad types of S. pneumoniae. Moreover, the vaccinated mice were protected from infections by a several types of S. pneumoniae, and the nasal vaccine exhibited protective efficacy in some strains which cannot be covered by the current vaccines. Thus, our findings demonstrated the nasally administered PspA nanogel vaccine effectively elicit a protective immunity and provide a broad protection against S. pneumoniae infections.

Pneumococcal disease and vaccination: recent changes to the schedule

Vaccination against pneumococcal disease has led to a significant drop in cases in the UK. Helen Sisson provides an overview of recent changes to the vaccination schedule Vaccination to protect against infectious diseases is a fundamental part of the practice nurse's role. The immunisation schedule in the UK frequently changes and this emphasises the need for nurses to remain familiar with what the changes are, and why they have occurred. The most recent change to the pneumococcal vaccination schedule at the start of this year provides an opportunity to reflect on the significance of infection with Streptococcus pneumoniae, which can cause non-invasive or invasive disease. The introduction of routine vaccination against pneumococcal disease for children has led to a significant drop in invasive disease in the population as a whole.

Morbidity and Mortality Due to Pneumococcal Disease in Children in Ecuador from 2005 to 2015.

Introduction:Studies have shown that pneumococcal disease significantly increases morbidity and mortality rates in children 5 years old and under. These infections constitute the main cause of preventable deaths in the world, considering the availability of vaccination. Considering that Ecuador is in a high incidence region, despite the introduction of the vaccine, this study aims to describe the burden of hospitalized pneumococcal disease and related mortality in our country between 2005 and 2015, to help decision-making processes for the health authorities.Methods:This cross-sectional study analyzes morbidity, mortality, and the situation in Ecuador caused by pneumococcal disease in children 5 years old and under between 2005 and 2015 using national databases.Results:A total of 163,852 cases of children 5 years old and under were reported to have been hospitalized due to pneumococcal-related diseases. Males comprised 54.7% of the cases and females 45.3%. In 36% of the cases, the patients were 1 year old or under. The mortality rate due to pneumococcal disease in Ecuador in children aged 5 and under decreased in 48% during 2005–2015.Conclusion:The decrease in mortality can be related to the introduction of the vaccine and an increase in access to health care by the general population in the country. It is important to study the specific impact of the vaccine in the reduction of morbidity and mortality of children in Ecuador.

The Impact of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccination on Invasive Pneumococcal Diseases in Children Under Five Year Old: An Article Review

The Impact of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccination on Invasive Pneumococcal Diseases in Children Under Five Year Old: An Article Review

Impact of 13Valent Vaccine for Prevention of Pneumococcal Diseases in Children and Adults at Risk: Possible Scenarios in Campania Region.

Pneumonias are the most frequent infectious diseases, characterized by a high prevalence especially among children and adults at risk. The socio-economic impact caused by Streptococcus pneumoniae is evaluated in terms of morbidity, death rate and hospitalizations. The aim of the study was to demonstrate the potential economic advantages by implementation of an active anti-pneumococcal 13-valent vaccine strategy in Campania region (Southern Italy) in two different categories of subjects, children (aged 0-12), and adults (aged 50- 79) at risk (hypertension, nephropathies, COPD and heart diseases). Vaccination costs were compared with costs necessary to treat avoidable diseases in the presence and absence of a vaccination program. Offering anti-pneumococcal 13-valent vaccine to the paediatric population was quantified as saving one million euros for Italian national health service in two years. In addition, offering anti-pneumococcal vaccine to adults at risk would generate a return of around 29 million euros. In both cases, offering anti-pneumococcal 13-valent vaccine was proven to be a helpful political health strategy, not only in consideration of a reduction of cases but also in view of the favourable economic impacts.

Burden of pneumococcal disease in children in Cuba before the introduction of a novel pneumococcal conjugate vaccine

# Background The Cuban heptavalent conjugate pneumococcal vaccine will be introduced for children beginning in 2020. We estimated the burden of pneumococcal cases and deaths in children 1-59 months in 2015. # Methods Mortality and morbidity attributable to pneumococcus were estimated for each of the three primary syndromes commonly associated with pneumococcus: pneumonia, meningitis, and invasive non-pneumonia, non-meningitis (NPNM). Vaccine randomized clinical trial data were used to estimate the proportion of pneumonia deaths attributable to pneumococcus. Data from Cuba were obtained from two domestic sources: National Bacterial Meningitis Surveillance System and the laboratory register from the National Reference Laboratory. Syndrome-specific pneumococcal mortality proportions were applied to all-cause pneumonia and meningitis death estimates prepared by the World Health Organization Maternal Child Epidemiology Estimation (WHO/MCEE) collaboration. The proportion of pneumonia cases attributable to pneumococcus was applied to estimates of all-cause clinical and severe pneumonia also prepared by the WHO/MCEE collaboration. Pneumococcal NPNM morbidity and mortality estimates were prepared using the ratio pneumococcal meningitis to pneumococcal invasive disease. Estimates were adjusted for HIV prevalence and access to health care. # Results In 2015, pneumococcus was estimated to cause 970 severe cases (uncertainty range, UR=692-1209) and 39 deaths (UR=23-59) among children 1-59 months. The estimated incidence rate of severe pneumonia was 149 (UR=112-170) per 100,000 children 1-59 months. The estimated case fatality ratio (CFR) was 2% (UR=1-2%). Over a period of one year, 22 deaths were attributed to pneumococcal pneumonia (UR=16-23), 9 (UR=14-19) to pneumococcal meningitis, and 8 (UR=3-17) to pneumococcal bacteremia. The CFR due pneumococcal meningitis was 18% (UR= 8-37%) in 2015. # Conclusions Reduced morbidity and mortality due to pneumococcal disease in Cuba could be achieved with the accelerated introduction of a novel PCV product in children.

2617. Increased Nasopharyngeal Pneumococcal Density During Asymptomatic Respiratory Virus Infection Is Associated with Subsequent Development of Acute Respiratory Illness

BackgroundIncreased density of nasopharyngeal (NP) pneumococcal colonization has been associated with invasive pneumococcal disease in children. However, factors that lead to increased pneumococcal density are poorly understood. We sought to determine whether viral detection during asymptomatic periods in young children was associated with increased NP pneumococcal density and the subsequent development of acute respiratory illness (ARI).MethodsUsing NP samples obtained during asymptomatic periods from children less than 3 years of age in the rural Peruvian Andes, we determined NP pneumococcal colonization density by quantitative polymerase chain reaction (qPCR) and identified respiratory viruses by RT–PCR. We examined the association between viral detection and pneumococcal density adjusting for relevant covariates using a multivariable quantile mixed effects regression model. We also assessed the association of pneumococcal density during asymptomatic periods in these children on the time to the next ARI using survival analysis.ResultsDuring asymptomatic periods, the presence of NP pneumococcal colonization was more common when respiratory viruses were detected. In addition, in the multivariable model, log10-transformed pneumococcal densities were significantly higher during asymptomatic periods when viruses were detected [median 4.52 (4.14, 5.01) P < 0.001], specifically human rhinovirus (HRV) [median 4.58 (4.27, 5.12), P < 0.001] and adenovirus (AdV) [median 4.21 (3.79, 4.91), P = 0.014], compared with when no virus was detected [median 3.16 (2.92, 3.73), Figure 1]. Increased pneumococcal density was also significantly associated with a higher rate of subsequent ARI (p = 0.008, Figure 2).ConclusionAmong young children, detection of respiratory viruses during asymptomatic periods was associated with increased pneumococcal colonization density, which, in turn, was associated with higher rate of subsequent ARI. Disclosures All authors: No reported disclosures.

2701. The Impact of Infant 13-valent Conjugate Pneumococcal Vaccination Program on Invasive Pneumococcal Disease in Children in British Columbia, Canada

BackgroundA significant reduction in invasive pneumococcal disease (IPD) has been reported following implementation of the 7-valent pneumococcal conjugate vaccine (PCV7) infant immunization program, but not much has been reported after introduction of the 13-valent vaccine (PCV13). This study represents the effect of PCV13 on IPD in British Columbia, Canada over a 14 year period (2002–2015).MethodsUsing provincial IPD laboratory surveillance data, we calculated the annual incidence following implementation of PCV7 (September 2004), and PCV13 (September 2010) in children less than 17 years of age. We also compared incidence rate ratios (IRR) against pre-PCV13 (2004–2010) and pre-PCV7 (2002–2003) baselines for overall and age-specific IPD rates using Poisson regression.ResultsA total of 697 cases were reported over the 14 year period. The overall annual incidence decreased from 10.9 cases per 100,000 population in 2002 to 4.64 cases per 100,000 population in 2015. While overall decline of IPD was 59% (IRR 0.41; 95% CI: 0.35–0.51) compared with baseline, this reduction was greatest after introduction of PCV7 (IRR 0.44; 95% CI: 0.37–0.53); the incremental change after introduction of PCV13 was non-significant (IRR 0.94; 95% CI: 0.78–1.13). The greatest reduction in IPD was in children <2 years of age (PCV13 vs baseline: IRR 0.19; 95% CI: 0.14–0.25), followed by children 3–5 years of age (PCV13 vs baseline: IRR 0.34; 95% CI: 0.21–0.56); no significant change was observed in 6–17 year olds.ConclusionWhile IPD rates have been significantly reduced since the introduction of the PCV vaccines, the impact of the additional 6 serotypes in the PCV13 vaccine is non-significant.Disclosures All authors: No reported disclosures.

Invasive Pneumococcal Disease in Children's Hospitals: 2014-2017.

The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed in the United States in 2010. We describe invasive pneumococcal disease (IPD) in children at 8 children's hospitals in the US from 2014 to 2017. Children with IPD occurring from 2014 to 2017 were identified from a prospective study. Demographic and clinical data, including results of any immune evaluation along with the number and dates of previous pneumococcal conjugate vaccines administered, were recorded on case report forms. Isolate serotypes were determined in a central laboratory. Pneumococcal conjugate vaccine doses were counted if IPD occurred ≥2 weeks after a dose. PCV13 serotypes accounted for 23.9% (115 out of 482) of IPD isolates from 2014 to 2017. Serotypes 3, 19A, and 19F accounted for 91% of PCV13 serotypes. The most common non-PCV13 serotypes were 35B, 23B, 33F, and 22F. An underlying condition was significantly (P < .0001) more common in children with IPD due to non-PCV13 serotypes (200 out of 367, 54.5%) than for children with PCV13 serotypes (27 out of 115, 23.5%). An immune evaluation was undertaken in 28 children who received ≥2 PCV13 doses before IPD caused by a PCV13 serotype. Only 1 was found to have an immunodeficiency. PCV13 serotypes (especially serotypes 3, 19A, and 19F) continue to account for nearly a quarter of IPD in US children 4 to 7 years after PCV13 was introduced. Underlying conditions are more common in children with non-PCV13 serotype IPD. Immune evaluations in otherwise healthy children with PCV13 serotype IPD despite receiving ≥2 PCV13 doses did not identify an immunodeficiency.

Evaluation of the impact of 13-valent pneumococcal conjugate vaccine immunization in children by surveillance of culture-confirmed pneumococcal disease: A prospective clinical microbiological study

The study aimed to investigate the impact of 13-valent pneumococcal conjugate vaccine (PCV13) immunization on the overall pneumococcal disease in children in Taiwan by surveillance of culture-confirmed pneumococcal disease (CCPD). This study was conducted in a medical center from 2012 to 2016. Clinical isolates of Streptococcus pneumoniae were prospectively collected from pediatric patients. Serotyping, multi-locus sequence typing, and antimicrobial susceptibility testing were performed. A total of 473 patients with CCPD, including 58 with invasive pneumococcal disease (IPD), were identified. The incidence of CCPD per 10,000 admissions decreased from 71.7 in 2012 to 27.0 in 2016. The proportion of additional PCV13 serotypes significantly decreased from 52.0% in 2012 to 21.7% in 2015 but increased slightly to 26.7% because of serotype 19A in 2016 (P < 0.0001). The proportion of non-vaccine serotypes (NVTs) increased significantly from 18.4% in 2012 to 66.7% in 2016, but the increase of the incidence of CCPD caused by NVTs was not considered significant (P = 0.0885). Genotyping identified predominant clones, ST6315A, ST8315B, and ST166/33823A, for major NVTs. The penicillin non-susceptibility of PCV13 serotypes was significantly higher than that of NVTs (P < 0.0001). Surveillance of CCPD appears superior to IPD alone for evaluation of the overall impact of pneumococcal immunization. Serotype replacement occurred quickly after the use of PCV13, while the incidence of NVT infection did not show a significant increase in children over the years. The gradual introduction of PCV13 into national immunization program is effective in reducing overall pneumococcal disease in children.

Invasive Pneumococcal Disease in Children Before and After the Introduction of Pneumococcal Conjugate Vaccine at a Regional Center in Kobe, Japan, 2002-2018

Invasive Pneumococcal Disease in Children Before and After the Introduction of Pneumococcal Conjugate Vaccine at a Regional Center in Kobe, Japan, 2002-2018

The clinical implication of serotype distribution and drug resistance of invasive pneumococcal disease in children: A single center study in southern Taiwan during 2010-2016.

The regional study of pediatric invasive pneumococcal disease (IPD) is still limited in Taiwan. The aim of this study is to update the epidemiologic data of pediatric IPD in Taiwan, focusing on the trend of non-13-valent pneumococcal conjugate vaccines (PCV13)-specific serotypes and antimicrobial susceptibility. This was a single-center retrospective study by chart reviewing and recruited patients aged <18 years who were reported having IPD between January 2010 and December 2016. Clinical manifestations, serotypes of pneumococcus and antimicrobial susceptibility were compared and analyzed. A total of 46 patients were enrolled in this study. Serotype 19 A was the most common serotype (32.6%) in pediatric IPD and significantly correlated with empyema. Non-PCV13-specific serotypes such as serotype 15, 15B, 15C and 22 were reported during this period. There was no mortality or significant morbidity associated with these emerging strains. Using the meningitis breakpoint of minimum inhibitory concentration (MIC), although it showed no significant linear trend of the prevalence of ceftriaxone non-susceptible pneumococcus (CNSP) (p=0.392), the prevalence of CNSP increased from 50% (11 over 22) before 2013 to 83% (20 over 24) after 2013 with statistical significance (p=0.027). The increase in the prevalence of CNSP using meningitis breakpoint was observed since 2013. For treating pneumococcal meningitis, empirical therapy with vancomycin and ceftriaxone is warranted. Although the non-PCV13-specific serotypes reported in our study caused no morbidity and mortality, further monitoring and surveillance are still recommended.

PMU20 CONSTRAINED OPTIMIZATION FOR IDENTIFYING THE COMBINATION OF PNEUMOCOCCAL VACCINATION SCHEMES WHICH MAXIMIZES QALY-GAINS OVER THE NEXT 10 YEARS IN BRAZIL

Several vaccines exist for managing pneumococcal-diseases in children and elderly. Some are age-specific (PHiD-CV, PPV-23) or used in both age-groups (PCV-13). Different vaccination schemes, prices and effects can be considered per vaccine and 9 different vaccination dosing schemes can be assembled across both age-groups. The economic question for Brazil is: which combination of vaccination dosing schemes for infants and elderly delivers maximum health gains within the next 10 years with limited annual vaccination budget increase? Constrained optimization (CO) is the most appropriate economic analysis to answer such question. It ranks vaccination schemes according to their health return on budgetary investments. While complying with constraints such as budget, logistics, and maximum vaccine coverage rates, CO identifies the combination of vaccination schemes that maximize the desired health outcome over a defined intervention period. CO for Brazil starts from the current situation: over 5 years of infant universal mass vaccination (UMV) with PHiD-CV 3-dose and an initial budget equaling the current one. Deterministic sensitivity analyses (SA) for budget increase, vaccine efficacy and waning are performed. With an annual budget increase of 10%, the consecutive sequence of (1) infant PHiD-CV, 3-dose, with elderly PPV-23, 2-dose with 5 years interval and (2) infant UMV replaced by PHiD-CV 4-dose, maximizes the overall QALY-gain (46,208 units over a period of 10 years). The gain in children is marginal (394 QALYs) while substantial in elderly (45,815 QALYs). SA showed most marked increase in QALY-gain with increasing proportion at-risk elderly, vaccination sequences however didn’t change. CO is a very helpful instrument for decision makers aiming for best return on investment when different options exist and many constraints must be considered. For Brazil, the highest public health gain with a limited annual vaccination budget increase is provided by UMV combining PHiD-CV in infants with PPV23 in elderly.

Impact of 13-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in children under 15 years old in Madrid, Spain, 2007 to 2016: The HERACLES clinical surveillance study

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Using the data from the HERACLES clinical surveillance study (2007–2016), we describe the population impact of the 13-valent pneumococcal conjugate vaccine (PVC13) on invasive pneumococcal disease (IPD) in children <15 years of age in the Community of Madrid, Spain. After six years of the inclusion of PCV13 in the vaccination calendar (2010–2016), and despite changes in the Regional Immunization Programme that limited its availability, the net benefit incidence rate (IR) of IPD fell by 70.1% (IRR 0.3 [95% CI: 0.22–0.4]; p ≤ 0.001), mainly due to a significant reduction (91%) in the PCV13 serotypes (IRR 0.09 [95% CI: 0.05–0.16], p ≤ 0.001). Furthermore, no significant changes were detected in the IR of IPD caused by non-PCV13 serotypes. The IRs of the aggressive, resistant and most prevalent serotype in the analysed population, the 19A serotype, dramatically decreased from the beginning to the end of the study (98%) [IRR 0.03 (95% CI: 0.00–0.19), p ≤ 0.001], to its almost total disappearance. Remarkably, this reduction led to a pronounced decline in the percentage of cefotaxime-resistant isolates and the incidence of meningitis cases. Assessment of the clinical impact revealed a reduction in the number of all clinical presentations of IPD, confirming the effectiveness of the PCV13. Finally, PCV13 detected by PCR is predicted to have a stronger impact than the one based on culture methods, which can overlook more than 20% of cases of IPD, mainly pleural empyemas.

Risk of invasive pneumococcal disease in children with sickle cell disease in the era of conjugate vaccines: a systematic review of the literature.

Pneumococcal conjugate vaccines (PCVs) are highly effective in preventing invasive pneumococcal diseases (IPD) in children, including those with sickle cell disease (SCD). A systematic review of the English literature published between 2000 and 2017 was undertaken to evaluate the serotype distribution, clinical presentation and outcomes of IPD in children with SCD in PCV programmes. We identified 475 potential studies and included 16 publications, involving 9438 children up to 22years of age with SCD and 182 IPD episodes (prevalence, 1·9%. 95% confidence interval [CI], 1·7-2·2%). Septicaemia was the most prevalent clinical presentation (84/137; 61%) followed by lower respiratory tract infection (39/137; 29%) and meningitis (12/137, 9%). More than half the serotypes associated with IPD (88/148; 59·5%) were not included in the 13-valent PCV; of these, 54% (44/82) were due to serogroup 15. The crude case fatality rate was 11·5% (21/182 cases; 95% CI, 7·3-17·1%). Most cases of IPD in children with SCD were due to serotypes that are not included in any of the licensed PCVs. IPD in children with SCD remains associated with high morbidity and mortality, highlighting the importance of strict adherence to daily penicillin prophylaxis. Until a serotype-independent pneumococcal vaccine becomes available, higher-valent PCVs should include serogroup 15 to protect this highly vulnerable group of children.

Cost-Effectiveness Comparison of Pneumococcal Conjugate Vaccines in Turkish Children

BackgroundThe 13-valent pneumococcal conjugate vaccine (PCV13) is used for universal infant vaccination in Turkey. ObjectivesTo assess the cost effectiveness of replacing PCV13 with pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). MethodsA Markov cohort model with monthly cycles following 1 cohort of infants over a 10-year time horizon was used. Local input parameters were obtained from published sources and expert consultation whenever possible. The model was adapted to estimate the health benefits and economic impact of each vaccine on invasive pneumococcal disease, pneumonia, and acute otitis media (AOM). An annual discount rate of 3% was used for benefits and costs (2016 euros). ResultsUnder base-case assumptions, vaccinating 1 birth cohort of 1 325 783 infants with PHiD-CV instead of PCV13 was predicted to have the same impact on meningitis and pneumonia, a similar impact on bacteremia (+30 cases), but greater reductions in AOM-related general practitioner visits (−34 955) and hospitalizations (−624). Assuming equal vaccine prices, PHiD-CV was predicted to be dominant over PCV13 (176 additional quality-adjusted life-years while saving €635 330 [discounted]). One-way sensitivity analysis indicated that varying the vaccine price differential had the largest effect on the incremental cost-effectiveness ratio, and then AOM parameters. Probabilistic sensitivity analysis predicted PHiD-CV to be dominant over PCV13 in 92.4% of simulations. ConclusionsAny difference in price between PHiD-CV and PCV13 is expected to be the key driver of vaccine choice for preventing childhood pneumococcal disease in Turkey. At price parity, PHiD-CV use is likely to be a dominant strategy over the use of PCV13.

Invasive pneumococcal diseases in children and adults before and after introduction of the 10-valent pneumococcal conjugate vaccine into the Austrian national immunization program.

BackgroundIn February 2012 the ten-valent pneumococcal conjugate vaccine (PCV10) with a 2+1 doses schedule (3, 5, 12 or 14 months of age) without catch-up vaccination was introduced in Austria. We assessed direct and indirect vaccine effects on invasive pneumococcal disease (IPD) by a population-based intervention study.MethodsThe study period was divided into pre- (2009–2011) and post-period (2013–2017, February), regarding 2012 as transition year. Outcomes were defined as PCV10 ST-IPD, the PCV10-related ST 6A and 19A IPD and non-PCV10 excluding ST 6A-/19A-IPD (NVT-IPD). We used national surveillance data and compared average monthly incidence rate (IR) between pre- and post-period among <5, 5–49 and ≥50 years old. Additionally, for the 5–49 and ≥50 years old, and the 50–59 and ≥60 years old, we analyzed monthly incidence data of the pre-, post-period, and estimated trend and level changes by using a segmented time-series regression.ResultsThe PCV-10 IPD was reduced by 58% (95% CI: 30%; 74%) and 67% (95% CI: 32%; 84%) among <5 and ≥50 years old; the reduction in ≥60 years was 71% (95% CI: 36%; 88%). There were no significant changes in the pre-post-rate or incidence trend of NVT-IPD in the <5 and ≥50 years old. ST-specific analyses revealed no ST 6A- and ST 19A IPD decline in any age-group, and a ST 8 IPD increase among ≥50 years old (IR ratio: 3.5; 95% CI: 1.7; 7.2). We found no vaccine effects among 5–49 years old.ConclusionsOur study adds to the evidence on direct and indirect protection of a childhood PCV10 vaccine program. Elderlies seem to benefit the most. Findings did not support PCV 10 cross-protection, but indicate replacement at least for ST 8 among the ≥50 years old. Follow-up analyses of IPD surveillance data are needed to fully characterize the magnitude of serotype replacement and further vaccine-attributable IPD reduction with time.

Risk factors associated with Streptococcus pneumonia carriage in children under five years old with acute respiratory infection in Niger.

IntroductionStreptococcus pneumonia is a leading cause of bacterial pneumonia, meningitis and sepsis in children, and pneumococcal carriage is an important source of horizontal spread of these pathogens within the community.MethodsA questionnaire was addressed to parents for the collection of sociodemographic and medical information. Nasopharyngeal swabbing was processed using a molecular method. We used logistic regression models to examine independent associations between pneumococcal carriage and potential risk factors. All associations with a p-value of < 0.25 in the bivariate regression analyses were subsequently entered in the multivariate regression model.ResultsA total of 637 children aged 1 to 59 months admitted for acute respiratory infection were included. The rate of respiratory virus carriage was 76%, whereas that of bacteria was 47% and that of bacteria-virus co-colonization was 42%. A bivariate analysis showed that carriage was not related to gender, father's or mother's education level, father's occupation, type of housing or lighting, or passive exposure to cigarette smoking in the house. It was also not linked to complete vaccination with PCV-13 or PPSV-23 and antibiotic treatment prior to hospitalization. A multivariate analysis showed that carriage was related to age greater than 3 months, maternal occupation, house flooring type, and co-colonization of another bacterium and virus.ConclusionThese results can be helpful to understand the dynamics of pneumococcal nasopharyngeal colonization; they confirm the interest of vaccinating infants before the age of 3 months with appropriate vaccine to prevent spread nasopharyngeal colonization and pneumococcal diseases in children.

A multicenter clinical study on 1 138 cases of invasive pneumococcal disease in children from 2012 to 2017

Objective: To explore the clinical features, the serotype distribution and drug resistance of the isolates in patient with invasive pneumococcal disease (IPD). Methods: By retrieving the laboratory information system in 18 children's hospitals from 2012 to 2017, the children with IPD were enrolled. Streptococcus pneumoniae (Spn) must be isolated from the sterile sites (blood, cerebrospinal fluid, hydrothorax and joint effusion etc.). The clinical characteristics, serotype, drug resistance, treatment and prognosis were reviewed and analyzed. According to the telephone follow up results, the patients were divided into death group and recovered group. The index as an independent risk factor of mortality was demonstrated by multivariate logistic regression analysis. Results: There were 1 138 children with IPD, including 684 male and 454 female. The proportion of male to female was 1.5∶1. The age ranged from one day to 16 years. The median age was 1 year 3 month. The majority was under 5 years of age (89.3%, n= 1 016), especially under 2 years of age (61.9%, n=704). In all cases, 88.2% (n=1 004) were community acquired infection. The infections included meningitis (n=446, 39.2%), pneumonia with bacteremia (n=339, 29.8%), and bacteremia without focus (n=232, 20.4%). Underlying diseases were found in 242 cases (21.3%). Co-infections were determined in 62 cases (5.4%) with mycoplasma, 27 cases (2.4%) with adenovirus and 34 cases with influenza virus (3.0%). The penicillin insensitivity (PNSP) rates in meningitis and non-meningitis isolates were 69.5% (276/397) and 35.9% (221/615), respectively. There were 81 strains serotyped, in which 93.8% (76/81) were covered by 13-valent protein-polysaccharide conjugate vaccine (PCV13). In the 965 patients who were followed up by phone call, 156 cases (16.2%) were confirmed dead. The independent risk factors for the death were under 2 years of age (OR=2.143, 95%CI 1.284-3.577, P=0.004), meningitis (OR=3.066, 95%CI 1.852-5.074, P<0.01), underlying disease (OR=4.801, 95%CI 2.953-7.804, P<0.01), septic shock(OR=3.542, 95%CI 1.829-6.859, P<0.01), disseminated intravascular coagulation (DIC) (OR=4.150, 95%CI 1.468-11.733, P=0.007), multiple organ failure (OR=12.693, 95%CI 6.623-24.325, P<0.01) and complications of central nervous system (OR=1.975, 95%CI 1.144-3.410, P=0.015). Conclusions: Most children with IPD were under 5 years of age, having underlying diseases and acquired the infection in community. The independent risk factors for death were under two years old, meningitis, underlying diseases and multiple organ failure. The problem of drug resistance was severe. The universal immunization of PCV13 would be effective to prevent IPD in Chinese children.

No Demonstrable Benefit of Penicillin in a Vaccinated Population of Children with Sickle Cell Disorder

UK and many National guidelines advise on the use of prophylactic antibiotics, immunisation and patient education to minimise the risk of severe infections by encapsulated organisms in patients with Sickle Cell Disorder. The UK vaccination schedule for sickle cell anaemia patients includes Pneumococcal, Meningococcal and Haemophilus influenzae type B (Hib) immunisation. Prophylactic Penicillin V is recommended as additional protection against Streptococcus pneumoniae (S.pneumoniae).In light of the findings in the papers by Oligbu et al, 2017, and Martin et al 2018, we aimed to retrospectively compare compliance with prophylactic Penicillin V against infection rates by S.pneumoniae,Neisseria meningitidis (N.meningitidis) and Hib . We hypothesised that the incidence of infections with IPD and other encapsulated organisms would be greater in patients who were not adherent with Penicillin V. Patients were considered compliant with prophylactic Penicillin V if 75% or more of their urine samples gave positive results.The study population consisted of 52 Sickle Cell patients, ranging from age 3 to 20years.Three patients were excluded as no urine samples had been collected from them in the 5 year period. Of the remaining 49 patients only 9 patients (18%) were had good adherence with Penicillin V over a 5 year period.100% of patients received prevenar vaccination (PCV-7 or PCV 13).73% received additional pneumovax.We retrospectively reviewed microbiology culture reports over a five year period. All microbiology reports were reviewed from the period, with the virulent encapsulated organisms of S.pneumoniae,N.meningitidis and Hib recorded, alongside any other bacterial infections.No patients had microbiological evidence of infection by virulent encapsulated bacteria. Six patients had cultures positive for other organisms: two Staphylococcus aureus positive sputum cultures, one Salmonella positive stool culture, two urine cultures positive for Escherichia coli, and one skin wound swab positive for Streptococcus pyogenes.Of the 6 organisms identified, 3 occurred in patients compliant with Penicillin V, and 3 occurred in patients who were non-compliant. Patients compliant with Penicillin V formed a small cohort (n=9), resulting in an apparently high incidence of infection (33%). In the non-compliant cohort (n=40), 8% had shown infection. Analysis by Fisher's Exact Test confirmed no significant difference in the incidence of infection between the two groups (p= 0.06).In a sickle cell disorder population where 82% of the patients were not 100% compliant with prophylactic Penicillin V, no significant encapsulated bacteria (S.pneumoniae,N.meningitidis or Hib) were cultured in a 5 year period in our cohort. Non-compliance with prophylactic Penicillin V was not associated with an increased incidence of infections by encapsulated organisms.The UK study (Oligbu et al) on IPD was performed in the PCV13 era and states a 49x increased risk of developing IPD and a 5x increase in mortality in children with sickle cell compared to their peers. However, most IPD cases were due to non-vaccine serotypes. A similar study from the US (Martin et al) found deaths only in the PCV7 cohort, it does not state if the patients were vaccinated with pneumovax 23.In conclusion 82% of children did not adhere to penicillin. We have not demonstrated any benefit in adhering to prophylactic penicillin. Adherence is poor and alternative approaches of standby antibiotics should be considered. We suggest focusing on vaccination as a preventative strategy is of more benefit. Martin OO, Moquist KL, Hennessy,JM, Nelson SC. Invasive pneumococcal disease in children with sickle cell disease in the pneumococcal conjugate vaccine era. Pediatr Blood Cancer. 2018;65:e26713. https://doi.org/10.1002/pbc.26713Oligbu G, Collins S , Streetly A, Dick, M, Ladhany, S. Risk of invasive pneumococcal disease in children with sickle cell disease in England: National observational cohort study, 2010 - 2015. Arch Dis Child 2017;102(Suppl1):A4-A4 DisclosuresNo relevant conflicts of interest to declare.