Non-vaccine Pneumococcal Serotypes Research Articles

P-619. Effectiveness of the 10-valent Pneumococcal Conjugate Vaccine (PCV10) on Hospital Admission due to Pneumonia among Nepalese Children

Abstract Background Streptococcus pneumoniae is the most common bacteria that causes pneumonia in children. The 10-valent pneumococcal vaccine (PCV10) has been introduced in the national immunization program (2+1 schedule: 6 and 10 weeks, and 9 months) in Nepal since 2015. The impact of PCV10 on hospital admission due to pneumonia is not well known in Nepal. Methods A cross-sectional study was carried out in Siddhi Memorial Hospital (SMH), Bhaktapur, Nepal, including hospital data from 2014 to 2022. SMH is the only pediatric general hospital in Bhaktapur district. The impact of PCV10 was assessed as a prevalence ratio analyzed with a log-binomial regression model. The prevalence ratio was calculated with the prevalence of hospital-admitted children due to chest x-ray confirmed pneumonia before and after the introduction of PCV10. The adjusted prevalence ratio (aPR) was measured in each year of the post-PCV10 period (2016 to 2022) by comparing the pre-PCV10 period (2014 and 2015) and adjusted by age, sex, and month of admission. Results A total of 10,897 children were admitted to the hospital during the study period (2014-2022). The prevalence of pneumonia was 20.4% (429/2,105) in the pre-PCV10 period and 10.5% (923/8,792) in the post-PCV10 period. The overall aPR declined; it was 0.50 (95%CI: 0.42-0.59) in 2019, just before the COVID-19 pandemic, and 0.32 (95%CI: 0.26-0.40) in 2022. Among children of 2 months to 2 years of age, we observed a 51.7% reduction in hospital admission due to pneumonia (aPR: 0.48, 95%CI: 0.37-0.61) in 2019 and a 72.6% reduction (aPR: 0.27, 95%CI: 0.19-0.40) in 2022. Conclusion We observed a significant decrease in hospital admissions due to pneumonia among children after the introduction of PCV10 in the national immunization program in Nepal. However, the surveillance of cases of pneumonia should be continued as the non-vaccine pneumococcal serotypes may emerge and hospital admissions due to pneumonia may go up in the future. Disclosures Konosuke Morimoto, MD, PhD, Pfizer: Grant/Research Support Koya Ariyoshi, MD, PhD, Pfizer: Grant/Research Support

The Molecular Epidemiology of Pneumococcal Strains Isolated from the Nasopharynx of Preschool Children 3 Years after the Introduction of the PCV Vaccination Program in Poland.

The genetic mechanisms of resistance, clonal composition, and the occurrence of pili were analyzed in 39 pneumococcal strains isolated from healthy children in the southeastern region of Poland. Strains with resistance to combinations of erythromycin, clindamycin, and tetracycline were found in clonal groups (CGs) related to Tennessee 23F-4 and Taiwan 19F-14 clones. Capsular switching possibly occurred in the Spain 9V-3 clone and its variants to serotypes 35B and 6A, as well as DLVs of Tennessee 23F-4 to serotype 23A. The double-locus variants of Colombia 23F-26 presented serotype 23B. The major transposons carrying the erythromycin and tetracycline resistance genes were Tn6002 (66.6%), followed by Tn916 (22.2%) and Tn2009 (11.1%). The macrolide efflux genetic assembly (MEGA) element was found in 41.7% of all erythromycin-resistant isolates. The majority of the isolates carrying the PI-1 gene belonged to the CGs related to the Spain 9V-3 clone expressing serotypes 35B and 6A, and the presence of both PI-1 and PI-2 was identified in CG4 consisting of the isolates related to the Taiwan 19F-14 clone expressing serotypes 19F and 19A. Importantly, in the nearest future, the piliated strains of serogroups 23B, 23A, and 35B may be of concern, being a possible origin of the emerging clones of piliated non-vaccine pneumococcal serotypes in Poland. This study reveals that nasopharyngeal carriage in children is an important reservoir for the selection and spreading of new drug-resistant pneumococcal clones in the community after the elimination of vaccine serotypes.

Comparison of specific in-vitro virulence gene expression and innate host response in locally invasive vs colonizer strains of Streptococcus pneumoniae

Among Rochester NY children, a dramatic increase in nasopharyngeal (NP) colonization by non-vaccine pneumococcal serotypes 35B and 15A occurred during years 2010-2015, after introduction of 13-valent pneumococcal conjugate vaccine (PCV13). In our population, serotype 35B strains colonized in the nasopharynx (NP) but infrequently caused acute otitis media (AOM) whereas serotype 15A strains displayed virulence, evidenced by causing AOM. To explain the virulence difference, virulence genes expression between 35B and 15A, as well as the host's immune response during asymptomatic colonization were analyzed. We investigated differences in regulation of 19 virulence genes for differences in virulence using RT-PCR in 20 35B and 14 15A strains and measured gene expression of 9 host innate cytokines in the NP to assess the mucosal inflammatory response during asymptomatic colonization. Comparing 35B versus 15A strains, genes for competence ComA and RrgC were upregulated; capsular (Cps2D) and virulence genes (PfbA, PcpA and PhtE) were downregulated among 35B strains. PavB, LytA, LytB, NanA, CiaR, PhtD, LuxS, PspA and pneumolysin (Ply) showed no difference. IL17 and IL23 gene expression were > tenfold higher during 35B compared to 15A strain asymptomatic colonization. Only IL23 showed significant difference. In the first 5 years after introduction of PCV13, serotype 35B strains emerged as asymptomatic colonizers and 15A strains emerged to cause AOM in young children. Various genes (PfbA, PcpA, Cps2D and PhtE) among tested in this analysis were downregulated in 35B whereas ComA and RrgC were significantly upregulated. For the host's cytokine response, IL23 proinflammatory response which is essential for the differentiation of Th17 lymphocytes in the NP of children with 35B strains was significantly higher than the response to 15A during asymptomatic colonization.

Antibiotic resistance of Streptococcus pneumoniae isolated from children in Moscow before
 and after the introduction of 13-valent pneumococcal conjugate vaccination

Introduction. The formation and spread of antibiotic-resistant Streptococcus pneumoniae isolates is a concern. After the thirteen-valent pneumococcal conjugate vaccine (PCV13) was added to the children’s immunization program in Russia in 2014, an important task is to monitor the resistance level to antimicrobials and the spectrum of circulating antibiotic-resistant pneumococcal serotypes. Materials and methods. The study included 708 nasopharyngeal pneumococcal isolates from children patients under 5 years who recovered from 2010 to 2018, received inpatient and outpatient care at the National Medical Research Center for Children’s Health (Moscow). The determination of sensitivity to antimicrobials was performed by the disk diffusion method. The MICs of penicillin, amoxicillin, and erythromycin were determined using the E-test method. Evaluation of the results was carried out according to the EUCAST-2019 criteria. Results. In total, 33 different serotypes were identified in the S. pneumoniae collection. Six predominant serotypes accounted for 68.6% of the total distribution and included serotypes: 19F, 6B, 23F, 14, 15B/C, 6A. In general, antimicrobial resistance ranged from 3.5% to chloramphenicol to 54.8% to tetracycline. The level of resistance to oxacillin, erythromycin, and clindamycin increased by 15-20% between 2010 and 2018. However, since 2016, there has established a prevalence level of 40-46%, this process is offset by an increase in the proportion of non-vaccine pneumococcal serotypes. Conclusion. A high level of resistance to penicillin and erythromycin remains. Monitoring the resistance level to antibiotics and the epidemiology of serotypes, clarifying the laws of formation of resistance, and its spread in a dynamically changing pneumococcal population is an important area of microbiology.

Successful intervention for overwhelming postsplenectomy infection caused by non-vaccine pneumococcal serotype 23A

The spleen plays an important role in the body’s immune defense against invasive infections, particularly those caused by encapsulated bacteria. Encapsulated bacterial infection in asplenic patients is a medical emergency called overwhelming postsplenectomy infection (OPSI) and has a mortality rate of 50–70%. Here, we report the case of a 51-year-old Asian man who complained of emesis and diarrhea as primary symptoms. He rapidly progressed to coma and was eventually diagnosed with OPSI (pyogenic ventriculitis/spondylitis) caused by non-vaccine pneumococcal serotype 23A. Aggressive management, including empiric antibiotic therapy, a staircase approach for intracranial pressure-targeted therapy and laminectomy/laminoplasty, resulted in a good recovery. Our report highlights that non-vaccine pneumococcal serotypes can cause disease in vaccinated patients.

Non-vaccine Pneumococcal Serotypes Among Children with Invasive Pneumococcal Disease

To report the percentage of non-vaccine pneumococcal serotypes and their antibiotic susceptibility pattern in children with invasive peumococcal disease. Invasive pneumococcal isolates of children <5 years during January 2007 to December 2016 were serotyped by a co-agglutination reaction and sequential multiplex polymerase chain reaction. Among the total 170 S. pneumoniae invasive isolates, 54 (31.8%) and 44 (25.9%) were the serotypes, which are not included in current 10-valent or 13-valent vaccines, respectively. Very low resistance was observed against penicillin (4.5%) and all isolates were susceptible to cefotaxime. One-fourth to one-third of the S. pneumoniae serotypes in under-five children with invasive pneumococcal disease are not covered by existing pneumococcal vaccines in India.

Pneumococcal Phenotype and Interaction with Nontypeable Haemophilus influenzae as Determinants of Otitis Media Progression.

All-cause otitis media (OM) incidence has declined in numerous settings following introduction of pneumococcal conjugate vaccines (PCVs) despite increases in carriage of nonvaccine pneumococcal serotypes escaping immune pressure. To understand the basis for the declining incidence, we assessed the intrinsic capacity of pneumococcal serotypes to cause OM independently and in polymicrobial infections involving nontypeable Haemophilus influenzae (NTHi) using samples obtained from middle ear fluid and nasopharyngeal cultures before PCV7/13 rollout. Data included samples from OM episodes (11,811) submitted for cultures during a 10-year prospective study in southern Israel and nasopharyngeal samples (1,588) from unvaccinated asymptomatic children in the same population. We compared data representing pneumococcal serotype diversity across carriage and disease isolates with and without NTHi coisolation. We also measured associations between the pneumococcal phenotype and the rate of progression from colonization to OM in the presence and absence of NTHi. Whereas pneumococcal serotype diversity was lower in single-species OM than in single-species colonization, levels of serotype diversity did not differ significantly between colonization and OM in mixed-species episodes. Serotypes differed roughly 100-fold in progression rates, and those differences were attenuated in polymicrobial episodes. Vaccine serotype pneumococci had higher rates of progression than nonvaccine serotypes. While serotype invasiveness was a weak predictor of the OM progression rate, efficient capsular metabolic properties-traditionally thought to serve as an advantage in colonization-predicted an enhanced rate of progression to complex OM. The lower capacity of nonvaccine serotypes to cause OM may partially account for reductions in all-cause OM incidence despite serotype replacement in carriage following rollout of PCVs.

Rapid replacement by non-vaccine pneumococcal serotypes may mitigate the impact of the pneumococcal conjugate vaccine on nasopharyngeal bacterial ecology

There is growing concern that interventions that alter microbial ecology can adversely affect health. We characterised the impact of the seven-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal carriage and the bacterial component of the nasopharyngeal microbiome during infancy. Newborns were recruited into three groups as follows: Group1 (n = 33) was the control group and comprised infants who received PCV7 after 6 months and came from unvaccinated communities. Group 2 (n = 30) came from unvaccinated communities and Group 3 (n = 39) came from vaccinated communities. Both group 2 and 3 received PCV7 at 2, 3 and 4 months. Culture and 16 S rRNA gene sequencing were performed on nasopharyngeal specimens collected at regular intervals from infants. Nasopharyngeal carriage of PCV7 serotypes in Group 1 was significantly higher than in Group 2 and 3 (p < 0.01). However, pneumococcal carriage remained comparable due to an expansion of non-vaccine serotypes in Groups 2 and 3. Determination of phylogenetic dis(similarities) showed that the bacterial community structures were comparable across groups. A mixed effects model showed no difference in community richness (p = 0.15) and Shannon α-diversity (p = 0.48) across the groups. Immediate replacement of pneumococcal vaccine serotypes with non-vaccine serotypes may mitigate the impact of PCV7 on nasopharyngeal bacterial community structure and ecology.

Pan-serotype Reduction in Progression of Streptococcus pneumoniae to Otitis Media After Rollout of Pneumococcal Conjugate Vaccines.

Reductions in otitis media (OM) burden following rollout of pneumococcal conjugate vaccines (PCVs) have exceeded predictions of vaccine impact. In settings with active surveillance, reductions in OM caused by vaccine-targeted pneumococcal serotypes have co-occurred with reductions in OM caused by other pathogens carried in the upper-respiratory tract of children. To understand these changes, we investigated the progression of vaccine-targeted and non-vaccine pneumococcal serotypes from carriage to OM before and after vaccine rollout. Nasopharyngeal carriage prevalence of pneumococcus was monitored in prospective studies of Bedouin and Jewish children <3 years old in southern Israel between 2004 and 2016. Incidence of OM necessitating middle-ear fluid culture (predominantly complex OM including recurrent, spontaneously-draining, non-responsive, and chronic cases) was monitored via prospective, population-based active surveillance. We estimated rates of pneumococcal serotype-specific progression from carriage to disease before and after rollout of PCV7/13, measured as OM incidence per carrier. We pooled serotype-specific estimates using Bayesian random-effects models. On average, rates of progression declined 92% (95% credible interval: 79-97%) and 80% (46-93%) for PCV7/13 serotypes among Bedouin and Jewish children <12 months old, respectively, and 32% (-58-71%) and 61% (-5-86%) among children aged 12-35m. For non-vaccine serotypes, rates of progression among Bedouin and Jewish children aged <12m declined 74% (55-85%) and 43% (4-68%), respectively. Vaccine-targeted and non-vaccine pneumococcal serotypes showed lower rates of progression to complex OM after rollout of PCV7/13. Early-life OM episodes historically associated with vaccine-serotype pneumococci may impact the susceptibility of children to OM progression.

The Saudi Thoracic Society pneumococcal vaccination guidelines-2016.

Streptococcus pneumoniae (pneumococcus) is the leading cause of morbidity and mortality worldwide. Saudi Arabia is a host to millions of pilgrims who travel annually from all over the world for Umrah and the Hajj pilgrimages and are at risk of developing pneumococcal pneumonia or invasive pneumococcal disease (IPD). There is also the risk of transmission of S. pneumoniae including antibiotic resistant strains between pilgrims and their potential global spread upon their return. The country also has unique challenges posed by susceptible population to IPD due to people with hemoglobinopathies, younger age groups with chronic conditions, and growing problem of antibiotic resistance. Since the epidemiology of pneumococcal disease is constantly changing, with an increase in nonvaccine pneumococcal serotypes, vaccination policies on the effectiveness and usefulness of vaccines require regular revision. As part of the Saudi Thoracic Society (STS) commitment to promote the best practices in the field of respiratory diseases, we conducted a review of S. pneumoniae infections and the best evidence base available in the literature. The aim of the present study is to develop the STS pneumococcal vaccination guidelines for healthcare workers in Saudi Arabia. We recommend vaccination against pneumococcal infections for all children <5 years old, adults ≥50 years old, and people ≥6 years old with certain risk factors. These recommendations are based on the presence of a large number of comorbidities in Saudi Arabia population <50 years of age, many of whom have risk factors for contracting pneumococcal infections. A section for pneumococcal vaccination before the Umrah and Hajj pilgrimages is included as well.

Nasopharyngeal carriage of Streptococcus pneumoniae and other bacteria in the 7th year after implementation of the pneumococcal conjugate vaccine in the Netherlands

After introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the infant national immunization program (NIP) in the Netherlands in 2006, Streptococcus pneumoniae strains of the non-vaccine serotype 19A emerged and became the dominant serotype in carriage in children and their parents. Similar patterns were observed in other European countries and the United States. Increases in carriage rates of Staphylococcus aureus and non-typeable (NT) Haemophilus influenzae were also observed. After switching of PCV7 to 10-valent vaccine (PCV10) in 2011, a new carriage surveillance study was performed in the winter of 2012/2013. Nasopharyngeal carriage of S. pneumoniae, H. influenzae, S. aureus, and Moraxella catarrhalis was determined by conventional culture in 330 PCV10-vaccinated 11-month-old children, 330 PCV7-vaccinated 24-month-old children, and their parents. Carriage prevalence was compared with similar carriage studies conducted in 2005, 2009, and 2010/2011. Although serotype 19A remained the most frequently carried pneumococcal serotype in children, prevalence of 19A significantly declined in PCV7-vaccinated 24-month-old children (14% to 8%, p=0.01), but less in PCV10-vaccinated 11-month-old children (12% to 9%, p=0.31). Carriage of H. influenzae remained stable at an elevated level (65% in 11-month-olds and 69% in 24-month-olds), while the carriage of S. aureus returned to pre-PCV7 levels in 11-month-old children (14% in 2010/2011 to 7% in 2012/2013), but not in 24-month-olds (remained at 7%). Our results might indicate a new balance between replacing non-vaccine pneumococcal serotypes and other potential pathogenic bacteria in nasopharyngeal carriage. Carriage studies are valuable tools in assessing vaccine effects on pathogens circulating in the population, for evaluation of PCV impact, and in predicting changes in respiratory and invasive disease.

Decline in Pneumococcal Nasopharyngeal Carriage of Vaccine Serotypes After the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Children in Atlanta, Georgia.

Streptococcus pneumoniae (SP) serotype distribution among nasopharyngeal (NP) carriage isolates changed significantly after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). We evaluated the impact on NP carriage and invasive disease of SP after the introduction of the 13-valent PCV (PCV13) in March 2010. NP swabs were collected from children 6-59 months of age in an emergency department from July 2010 to June 2013. After broth enrichment, samples were cultured for SP and isolates were serotyped. Clinical and immunization records were reviewed. Findings during 6 sequential 6-month study periods were compared. Surveillance isolates of invasive disease isolates were reviewed. A total of 2048 children were enrolled, and 656 (32%) were SP carriers. Mean age of carriers was 27 months, 54% were males. Carriage was higher among day-care attendees (P < 0.01) and children with respiratory tract illnesses (P < 0.5) and otitis media (P < 0.01). Commonly carried serotypes included 35B (15.2%), 15B/C (14.2%), 19A (9.6%), 11A (8%), 23B (5.6%), 6C (5.3%), 21 (5%), and 15A (5%); 13.9% were PCV13 serotypes. The proportion of children with SP carriage remained stable but the serotype distribution changed during the study period. Among carriers, PCV13 serotypes declined from 29% (36/124) to 3% (3/99; P < 0.0001), predominantly because of decline of serotype 19A from 25.8% (32/124) to 3% (3/99; P < 0.0001); non-PCV13 serotypes (excluding 6C) increased from 68.4% (78/114) to 97% (95/98; P < 0.0001); serotype 35B significantly increased from 8.9% (11/124) to 25.3% (25/99; P < 0.05). Nonsusceptibility to ceftriaxone declined from 22.6% (28/124) to 0% (0/99; P < 0.0001), with a similar decline in penicillin nonsusceptibility. Introduction of PCV13 for universal infant use was associated with significant reductions in nasopharyngeal carriage of PCV13 serotypes and resistant strains. Carriage of non-PCV13 serotypes increased modestly, particularly serotype 35B. Further investigation is warranted to determine whether nonvaccine pneumococcal serotypes carried in the nasopharynx are associated with significant replacement disease.

Impact of pneumococcal conjugate vaccines on childhood otitis media in the United Kingdom

BackgroundStudies have demonstrated a reduction for otitis media (OM) following the introduction of seven-valent pneumococcal conjugate vaccine (PCV7), but this has not been evaluated in the United Kingdom (UK). Moreover, there are limited data on any additional impact of PCV13 introduction in 2010. MethodsWe conducted an observational cohort study to investigate the trends in OM incidence and associated antibiotic prescriptions in children aged <10 year-olds during 2002–2012 using a national primary care database. Three time-periods were defined to estimate monthly incidence: pre-PCV7 (January 2002–August 2006), post-PCV7 (September 2007–March 2010), and post-PCV13 (April 2011–December 2012). ResultsOverall annual OM incidence declined by 51.3% from 135.8 episodes/1000 person-years in 2002 to 66.1 episodes/1000 person-years in 2012; antibiotic prescription rates for OM declined by 72.9% from 57.9 prescriptions/1000 person-years to 15.7 prescriptions/1000 person-years, respectively. PCV7 introduction was associated with significant decline in OM rates across all age-groups (21.8%; 95% CI, 20.2–23.4), including <2 year-olds (19.8%; 95% CI, 16.0–23.5%); 2–4 year-olds (23.0%; 95% CI, 20.4–25.4%) and 5–9 year-olds (20.2%; 95% CI, 17.6–22.7%). There was an additional significant reduction in OM (18.5%; 95% CI, 16.7–20.2%) and associated antibiotic prescribing (12.2%; 95% CI, 8.6–15.6%) after the introduction of PCV13 across all age-groups. ConclusionThe introduction of PCV7 was associated with a 22% significant reductions in OM in children aged <10 year-olds with an additional 19% reductions after PCV13 introduction. These declines are equivalent to 592,000 and 15,700 fewer consultations and OM-related hospitalizations, respectively, in England and Wales every year. Although the continuing decline in OM rates in our study suggests that further reduction may continue to occur, it is important to monitor long-term trends in all pneumococcal diseases, including OM and pneumonia, because of increasing replacement of non-vaccine pneumococcal serotypes in carriage and disease.

Evolution of pneumococcal infections in adult patients during a four-year period after vaccination of a pediatric population with 13-valent pneumococcal conjugate vaccine

To describe the distribution of vaccine and non-vaccine pneumococcal serotypes from adult patients for different clinical scenarios, after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV-13) for children. This was a prospective study of pneumococcal infections in adult patients (January 2010 to April 2014) in Hospital Son Llàtzer, Mallorca (Spain). Two different periods of time were compared, the first before (first period) and the second after (second period) the introduction of PCV-13. Information related to clinical characteristics, outcomes of infection, pneumococcal serotypes, and antibiotic susceptibility was collected. We studied 407 episodes (371 patients), 201 in the first period and 206 in the second period. The majority of patients were male; the median patient age was 68 (range 15-99) years. Infections due to PCV-13 serotypes decreased from 59.7% to 47.6% (p=0.014), mainly serotypes 3, 7, 18C, 19F, and 23F. In the second period, PCV-13 serotypes were the cause of pneumonia in 58.2% of cases and in 40.8% of invasive infections, but these serotypes were not related with any outcome variable. No differences in hospital or intensive care unit admission, severity, or mortality were observed between the two periods. Susceptibility to penicillin (98.2% vs. 95.1%, p=0.03) and amoxicillin (96.5% vs. 91%, p=0.007) was slightly higher in the first period. Although a reduction in infections due to vaccine serotypes was observed, close to half of infections in adult patients were caused by PCV-13 serotypes. Even after pediatric vaccination with PCV-13, vaccine serotypes were still responsible for most pneumonia and invasive disease, underscoring the importance of implementing current guidelines and extending vaccination to other risk groups.

Aetiology of paediatric pneumonia after the introduction of pneumococcal conjugate vaccine

We describe the aetiology of community-acquired pneumonia in children before and after the introduction of the pneumococcal conjugate vaccination (PCV) programme in 2006.Prospective studies were conducted in 2001–2002 (pre-vaccine) and 2009–2011 (post-vaccine) of children aged 0–16 years with radiologically confirmed pneumonia seen in hospital. Investigations included culture, serology, immunofluorescence antibody and urine antigen testing, with an increased use of PCR assays and expanded panels of pathogens in the post-vaccine study.241 and 160 children were enrolled in the pre- and post-vaccine studies, respectively (73% aged <5 years). Identification of a causative pathogen was higher post-vaccination (61%) than pre-vaccination (48.5%) (p=0.019). Rates of bacterial infections were not different between post- and pre-vaccine studies (17.5% versus 24%, p=0.258). Viral (31%) and mixed (12.5%) infections were found more often post-vaccination (19.5%, p=0.021) than pre-vaccination (5%, p=0.015). Rates of identified pneumococcal infections were comparable between pre- and post-vaccine studies (14.7% versus 17.4%, p=0.557). Diagnosis of pneumococcal infection post-vaccination improved when PCR was used compared to culture (21.6% versus 6%, p=0.0004). Serotypes included in PCV13 but not PCV7 were identified in 75% (18 out of 24) post-vaccination.Infection with nonvaccine pneumococcal serotypes continues to be a significant cause of pneumonia in children in the UK.

Impact of the emergence of non-vaccine pneumococcal serotypes on the clinical presentation and outcome of adults with invasive pneumococcal pneumonia

The introduction of the 7-valent pneumococcal conjugate vaccine in children has led to a change in the pattern of pneumococcal serotypes causing pneumococcal disease. The aim of this study was to compare the clinical presentation and outcome of invasive pneumococcal pneumonia (IPP) in adults between the pre and post-vaccine era. We have conducted an observational study of all adults hospitalized with IPP, from 1996 to 2001 (pre-vaccine period), and from 2005 to 2009 (post-vaccine period). Incidence, serotype distribution and clinical data were compared between both periods. A total of 653 episodes of IPP were diagnosed. The overall incidence of IPP increased from 14.2 to 17.9 cases per 100 000 population-year (p 0.003). In the post-vaccine period IPP caused by vaccine serotypes decreased (–36%; 95% CI, –52 to –15) while IPP caused by non-vaccine serotypes increased (71%; 95% CI, 41–106). IPP in the post-vaccine period was associated with higher rates of septic shock (19.1% vs. 31.1%, p <0.001). Among patients aged 50–65 years there was a trend towards a greater proportion of case-fatalities (11.6–23.5%, p 0.087). Independent risk factors for septic shock were IPP caused by serotype 3 (OR 2.38; 95% CI, 1.16–4.87) and serotype 19A (OR 6.47, 95% CI, 1.55–27). Serotype 1 was associated with a lower risk of death (OR 0.1; 95% CI, 0.01–0.78). In conclusion, the incidence of IPP in the post-vaccine period has increased in our setting, it is caused mainly by non-vaccine serotypes and it is associated with higher rates of septic shock.

Child pneumonia: beyond pneumococcal vaccine and 2015.

Impressive gains have been made in child survival over the last decade, including a reduction in deaths due to childhood pneumonia.1 Pneumonia nonetheless remains the main reason why many children still do not live to enjoy their fifth birthday. The Global Coalition Against Child Pneumonia was established in 2009 to provide leadership for World Pneumonia Day, marked each year on November 12 to encourage donors, policy makers, health care providers and the general public to combat the disease. Pneumonia is caused by a wide range of pathogens, the relative importance of which varies between settings. Immunisation has played an important role in preventing pneumonia deaths due to measles, pertussis and Haemophilus influenzae. The availability of the pneumococcal conjugate vaccine, and its support for implementation in high mortality settings by the Global Alliance for Vaccines and Immunizations, has resulted in great optimism as it is likely to prevent a large number of deaths due to pneumococcal pneumonia (and meningitis). However, pneumonia-related deaths in neonates and children will continue to occur, including those due to non-vaccine pneumococcal serotypes, other common bacteria and viruses. The wide range of pathogens and limitations in current diagnostics present major challenges for investments in research and programme implementation for pneumonia. These have been neglected relative to research and programmes for malaria and the human immunodeficiency virus (HIV), which have been based on comprehensive approaches and evidence, and are strong in preventive and curative interventions. For example, malaria has been the focus of 22% of the randomised trials conducted in child health in developing countries in the last decade, while pneumonia represents less than 4%.2 Moreover, malaria research has been integrated into programmes rapidly, with resulting unprecedented gains in disease control and reductions in child mortality due to malaria. For pneumonia a similar approach is needed that goes beyond the introduction of the pneumococcal vaccine. A balanced and comprehensive approach would emphasise other preventive strategies: nutrition and breastfeeding, reduction in indoor air pollution, hand-washing and improved case management. Curative interventions include addressing the rising rates of bacterial resistance, models of community care, the role of zinc, improved outcomes for high-risk patients (malnourished, HIV-infected and neonates), as well as wider availability of oxygen therapy and other methods of respiratory support. Controlled treatment trials in the last decade have established the safety of different approaches to community-based case management of World Health Organization defined non-severe and severe pneumonia in some settings.3,4 Most of these have been in urban and peri-urban areas in south Asia, characterised by low mortality and a high prevalence of viral infection. The challenge is to conduct research in populations with higher mortality, a higher prevalence of bacterial pneumonia, malnutrition and HIV, and where access to care is more challenging. The heterogeneity of populations and uncertainties about the global applicability of research are illustrated by trials evaluating zinc adjunct therapy, where the findings have not been consistent between settings. A recent randomised trial in Uganda reported significant benefit of zinc adjunct therapy with regard to mortality, particularly in HIV-infected children.5 Understanding where evidence does and does not apply is a challenge for balanced and comprehensive pneumonia control programmes. Understanding the social and health system determinants of pneumonia causation and death is crucial to developing comprehensive approaches. Incorporating comprehensive approaches in national plans for child survival is the way to proceed. It won’t be as easy as a single vaccine, but a more comprehensive approach will take countries beyond this—and 2015—in tackling pneumonia.

Safety and Immunogenicity of a 13-valent Pneumococcal Conjugate Vaccine in Healthy Infants and Toddlers Given With Routine Pediatric Vaccinations in Canada

The global distribution of pneumococcal disease and emergence of nonvaccine pneumococcal serotypes prompted the development of a 13-valent pneumococcal conjugate vaccine (PCV13), with broader coverage than 7-valent PCV (PCV7). This study compared compatibility of PCV13 and PCV7 with concurrently administered diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b vaccine, and meningococcal C conjugate vaccine (menC), and assessed the safety and immunogenicity of PCV13. In this double-blind, randomized trial, children received PCV7 or PCV13 at 2, 4, 6, and 12 months with routine vaccinations. One month following the infant series and toddler dose, the responses to Hib, pertussis, menC, and specific pneumococcal serotypes were measured. Safety and tolerability were assessed daily for 4 days by parents. Subjects received PCV13 (n = 300) or PCV7 (n = 303); immunogenicity assessment was completed in 265 and 268 subjects, respectively. There were no statistically significant differences between the groups in responses to Hib, pertussis, or menC after primary or booster vaccinations. More than 95% of subjects in the PCV13 group produced >0.35 μg/mL antibody to each pneumococcal serotype 1 month after the third dose, except with serotypes 23F (90%), 3 (80%), and 5 (87%). After the fourth dose, 98% to 100% of subjects achieved serotype-specific antibody concentrations >0.35 μg/mL, except for serotype 3 (85%). Safety and tolerability did not differ between groups with respect to local or systemic side effects. Responses to routine childhood vaccines did not differ with PCV7 or PCV13 coadministration. Serotype-specific pneumococcal antibody concentrations were protective. The safety profile of PCV13 was favorable.

Increase in invasive nonvaccine pneumococcal serotypes at two hospitals in Barcelona: was replacement disease to blame?

To describe an increase in the incidence of invasive pneumococcal disease (IPD) caused by serotypes not contained in the heptavalent pneumococcal conjugate vaccine (PCV7) in children in two hospitals in Barcelona with different vaccine uptake. Cumulative incidences of IPD, vaccine and nonvaccine serotypes (NVSTs), and main clinical presentations before (1998-2001) and after vaccine introduction (2005-2008) were compared. The incidence of IPD in children aged <2 years at Hospital Germans Trias i Pujol covering a population in which PCV7 was not widely used showed a nonsignificant increase from 29.9 to 58.8 per 100,000 child-years between both periods. Following vaccine introduction, there was a 2.5-fold increase in IPD caused by NVSTs in children aged <5 years. Analysis of trends in the almost fully vaccinated population of Hospital de Barcelona revealed a nonsignificant reduction in IPD incidence in children aged <2 years from 63.1 to 26.0 per 100,000 child-years. NVSTs in children aged <5 years showed a nonsignificant 1.7-fold increase in the vaccine period at this centre. The paradoxical increase in invasive infections caused by NVSTs in these populations with different vaccine use suggests that these changes were not driven only by PCV7.

Rebound in the incidence of pneumococcal meningitis in northern France: effect of serotype replacement

To determine whether the recent emergence of nonvaccine pneumococcal serotypes has affected the incidence of pneumococcal meningitis in children a few years after the introduction of the heptavalent pneumococcal conjugate vaccine. We conducted a multicentre retrospective cohort study from 2005 to 2008 in all hospitals with paediatric units in northern France. It included all patients < 18 years of age who were admitted for laboratory-confirmed pneumococcal meningitis during the study period. Data were collected from medical files and laboratory records at each hospital and compared with the regional hospital discharge codes. We assessed global and age-specific incidence rates of pneumococcal meningitis from 2005 through 2008, compared them with those from the prevaccine era (2000-2002) and evaluated pneumococcal serotypes. In all, 41 cases were found during the study period. The incidence rate of pneumococcal meningitis varied from 0.8/100,000 children < 18 years in 2005 to 1.8/100,000 children in 2008 (2.2-fold increase, p = 0.06); and from 1.8 to 11.9/100,000 children < 2 years (6.5-fold increase, p = 0.004). This increase was caused by nonvaccine pneumococcal serotypes. The incidence of pneumococcal meningitis in infants has rebounded in northern France during the pneumococcal conjugate vaccine programme, with the emergence of nonvaccine pneumococcal serotypes.