Effectiveness Of Pneumococcal Conjugate Vaccine Research Articles

Impact of pneumococcal conjugate vaccine 13 introduction on severe lower respiratory tract infections associated with respiratory syncytial virus or influenza virus in hospitalized children in Ulaanbaatar, Mongolia

ObjectivesLimited data indicate a beneficial effect of pneumococcal conjugate vaccines (PCVs) on respiratory syncytial virus (RSV) and influenza infections in young children. We evaluated the impact of 13-valent PCV (PCV13) introduction on the incidence of severe lower respiratory tract infections (LRTIs) associated with RSV or influenza in hospitalized children. MethodsOur study was restricted to children aged <2 years with arterial oxygen saturation <93% and children with radiologically confirmed pneumonia nested in a pneumonia surveillance project in four districts of Ulaanbaatar city, Mongolia. We tested nasopharyngeal swabs collected on admission for RSV and influenza using quantitative reverse transcription-polymerase chain reaction. The impact of PCV13 on the incidence of LRTI outcomes associated with RSV or with influenza for the period April 2015-March 2020 was estimated. Incidence rate ratios comparing pre- and post-vaccine periods were estimated for each outcome for each district using negative binomial models and for all districts combined with a mixed-effects negative binomial model. Adjusted models accounted for seasonality. Sensitivity analyses were conducted to assess the robustness of our findings. ResultsAmong 5577 tested cases, the adjusted incidence rate ratios showed a trend toward a reduction in RSV-associated outcomes: all LRTIs (0.77, 95% confidence interval [CI] 0.44-1.36), severe LRTIs (0.88, 95% CI 0.48-1.62), very severe LRTIs (0.76, 95% CI 0.42-1.38), and radiologically confirmed pneumonia (0.66, 95% CI 0.32-1.38) but inconsistent trends in outcomes associated with influenza. ConclusionsNo significant reductions were observed in any outcomes associated with RSV and influenza after PCV introduction.

Effect of pneumococcal conjugate vaccines on viral respiratory infections: a systematic literature review.

In addition to preventing pneumococcal disease, emerging evidence indicates that pneumococcal conjugate vaccines (PCVs) might indirectly reduce viral respiratory tract infections (RTI) by affecting pneumococcal-viral interactions. We performed a systematic review of interventional and observational studies published during 2000-2022 on vaccine efficacy/adjusted effectiveness (VE) and overall effect of PCV7, PCV9, PCV10, or PCV13 against viral RTI. Sixteen of 1671 records identified were included. Thirteen publications described effects of PCVs against viral RTIs in children. VE against influenza ranged between 41-86% (n=4), except for the 2010-2011 influenza season. In a randomized controlled trial, PCV9 displayed efficacy against any viral RTI, human seasonal coronavirus, parainfluenza, and human metapneumovirus. Data in adults were limited (n=3). PCV13 VE ranged between 4-25% against viral lower RTI, 32-35% against COVID-19 outcomes, 24-51% against human seasonal coronavirus, and 13-36% against influenza A lower RTI, with some 95%CI spanning zero. No protection was found against adenovirus or rhinovirus in children or adults. PCVs were associated with protection against some viral RTI, with the strongest evidence for influenza in children. Limited evidence for adults was generally consistent with pediatric data. Restricting public health evaluations to confirmed pneumococcal outcomes may underestimate the full impact of PCVs.

Effect of Pneumococcal Conjugate Vaccine on Pneumonia Incidence Rates among Children 2-59 Months of Age, Mongolia, 2015-2021.

Starting in June 2016, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced into the routine immunization program of Mongolia by using a 2+1 dosing schedule, phased by district. We used prospective hospital surveillance to evaluate the vaccine's effect on pneumonia incidence rates among children 2-59 months of age over a 6-year period. Of 17,607 children with pneumonia, overall adjusted incidence rate ratios showed decreased primary endpoint pneumonia, very severe pneumonia, and probable pneumococcal pneumonia until June 2021. Results excluding and including the COVID-19 pandemic period were similar. Pneumonia declined in 3 districts that introduced PCV13 with catch-up campaigns but not in the 1 district that did not. After PCV13 introduction, vaccine-type pneumococcal carriage prevalence decreased by 44% and nonvaccine-type carriage increased by 49%. After PCV13 introduction in Mongolia, the incidence of more specific pneumonia endpoints declined in children 2-59 months of age; additional benefits were conferred by catch-up campaigns.

Prevalence of prolonged otitis media with effusion among 2 to 3 years old Cameroonian children in the era of 13-valent pneumococcal conjugate vaccines

ObjectivesThere is data scarcity on the overall effects of pneumococcal conjugate vaccines (PCVs) on otitis media (OM) in low- and middle-income countries. The impact of the 13-valent PCV (PCV13) program on OM was evaluated in Cameroon where infant vaccination was implemented in July 2011 using a 3-dose primary series at 6, 10 and 14 weeks of age. MethodsThrough community-based surveillance, we used a retrospective cohort study design to assess OM prevalence among PCV13-vaccinated children aged 24 to 36 months in 2015. This was compared with a 2013 age-matched cohort of PCV13-unvaccinated children. OM was diagnosed by clinical inspection for chronic suppurative OM (CSOM) and tympanometry for OM with effusion (OME). CSOM was defined as draining of the middle ear with duration of more than 2 weeks and prolonged OME was defined as a flat ‘type B’ tympanogram. PCV13-vaccinated and PCV13-unvaccinated cohorts were compared by calculating prevalence odds ratios for OM and baseline characteristics. ResultsAltogether, 111 OM cases were identified; 42/433 (9.7%) in the PCV13-unvaccinated in 2013 and 69/413 (16.7%) in the PCV13-vaccinated cohort in 2015. In the 2013 baseline survey, 3/433 (0.7%) children were identified with unilateral CSOM compared to 9/413 (2.2%) in the PCV13-vaccinated cohort in 2015. Bilateral prolonged OME was diagnosed in 7/433 (1.6%) PCV13-unvaccinated children and in 12/413 (2.9%) in PCV13-vaccinated children. Proportions of children with unilateral prolonged OME were 31/433 (7.2%) in the PCV13-unvaccinated group compared with 48/413 (11.6%) in the PCV13-vaccinated group. Multivariate logistic regression analysis showed evidence that PCV13-vaccinated children in 2015 had 40% less risk of contracting OM compared to PCV13-unvaccinated children in 2013 (adjusted prevalence odds ratios = 0.60 [95% confidence interval: 0.38 to 0.94], P = 0.025). Additionally, attributable proportion estimates show that, 58% of OM infections among the PCV13-vaccinated group would still have occurred despite PCV13 vaccination. ConclusionOur findings provide significant evidence on the effect of PCV13 in decreasing OM or OME among children in this age group. It also supports justification for government's continuation of PCV13 immunization program in the absence of GAVI's funding. Further research is needed to assess the long-term impact of the PCV13 program on in OM Cameroon.

Preclinical evaluation of an investigational 21-valent pneumococcal conjugate vaccine, V116, in adult-rhesus monkey, rabbit, and mouse models.

Despite the widespread effectiveness of pneumococcal conjugate vaccines on the overall incidence of invasive pneumococcal disease, the global epidemiological landscape continues to be transformed by residual disease from non-vaccine serotypes, thus highlighting the need for vaccines with expanded disease coverage. To address these needs, we have developed V116,an investigational 21-valent non-adjuvanted pneumococcal conjugate vaccine (PCV),containingpneumococcal polysaccharides (PnPs) 3, 6A, 7F, 8, 9N, 10A, 11A,12F, 15A, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, 35B, anda de-O-acetylated 15B(deOAc15B) individually conjugated to the nontoxic diphtheria toxoid CRM197 carrier protein. Preclinical studies evaluated the immunogenicity of V116 inadult monkeys, rabbits, and mice. Following one dose, V116 was found to be immunogenic in preclinical animal species and induced functional antibodies for all serotypes included in the vaccine, in addition to cross-reactive functional antibodies to serotypes 6C and 15B. In these preclinical animal studies, the increased valency of V116 did not result in serotype-specific antibody suppression when compared to lower valent vaccines V114 or PCV13. In addition, when compared with naïve controls, splenocytes from V116 to immunized animals demonstrated significant induction of CRM197-specific T cells in both IFN-γ and IL-4 ELISPOT assays, as well as Th1 and Th2 cytokine induction through in vitro stimulation assays, thus suggesting the ability of V116 to engage T cell dependent immune response pathways to aid in development of memory B cells. V116 also demonstrated significant protection in mice from intratracheal challenge with serotype 24F, a novel serotype not contained in any currently licensed vaccine.

Effect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004–20: a national surveillance study

BackgroundEpidemiological studies are necessary to explore the effect of current pneumococcal conjugate vaccines (PCVs) against antibiotic resistance, including the rise of non-vaccine serotypes that are resistant to antibiotics. Hence, epidemiological changes in the antimicrobial pattern of Streptococcus pneumoniae before and during the first year of the COVID-19 pandemic were studied.MethodsIn this national surveillance study, we characterised the antimicrobial susceptibility to a panel of antibiotics in 3017 pneumococcal clinical isolates with reduced susceptibility to penicillin during 2004–20 in Spain. This study covered the early and late PCV7 periods; the early, middle, and late PCV13 periods; and the first year of the COVID-19 pandemic, to evaluate the contribution of PCVs and the pandemic to the emergence of non-vaccine serotypes associated with antibiotic resistance.FindingsSerotypes included in PCV7 and PCV13 showed a decline after the introduction of PCVs in Spain. However, an increase in non-PCV13 serotypes (mainly 11A, 24F, and 23B) that were not susceptible to penicillin promptly appeared. A rise in the proportion of pneumococcal strains with reduced susceptibility to β-lactams and erythromycin was observed in 2020, coinciding with the emergence of SARS-CoV-2. Cefditoren was the β-lactam with the lowest minimum inhibitory concentration (MIC)50 or MIC90 values, and had the highest proportion of susceptible strains throughout 2004–20.InterpretationThe increase in non-PCV13 serotypes associated with antibiotic resistance is concerning, especially the increase of penicillin resistance linked to serotypes 11A and 24F. The future use of PCVs with an increasingly broad spectrum (such as PCV20, which includes serotype 11A) could reduce the impact of antibiotic resistance for non-PCV13 serotypes. The use of antibiotics to prevent co-infections in patients with COVID-19 might have affected the increased proportion of pneumococcal-resistant strains. Cefotaxime as a parenteral option, and cefditoren as an oral choice, were the antibiotics with the highest activity against non-PCV20 serotypes.FundingThe Spanish Ministry of Science and Innovation and Meiji-Pharma Spain.TranslationFor the Spanish translation of the abstract see Supplementary Materials section.

Effect of pneumococcal conjugate vaccine on prevalence of otitis media with effusion among children in Vietnam

PurposeOtitis media with effusion (OME) is common in young children and is associated with Streptococcus pneumoniae infection. We aimed to determine the impact of pneumococcal conjugate vaccine (PCV) introduction on the prevalence of OME and OME associated with vaccine-type (VT) or non-VT. MethodsPopulation-based cross-sectional surveys were conducted in pre- (2016) and post-PCV periods (2017, 2018, and 2019) at selected communes in Nha Trang, Vietnam. For each survey, we randomly selected 60 children aged 4–11 months and 60 aged 14–23 months from each commune. Nasopharyngeal sample collection and tympanic membrane examination by digital otoscope were performed. S. pneumoniae was detected and serotyped by lytA qPCR and microarray. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using Firth’s logistic regression, stratified by age group. ResultsOver the four surveys, 2089 children had a bilateral ear examination. Compared to pre-PCV, the prevalence of OME reduced in 2018 (OR 0.51, 95 %CI 0.28–0.93) and in 2019 (OR 0.53, 95 %CI 0.29–0.97) among the <12-month-olds, but no significant reduction among the 12–23-month-olds. The prevalence of OME associated with VT pneumococcus decreased in 2018 and 2019 (2018: OR 0.14, 95 %CI 0.03–0.55; 2019: OR 0.20, 95 %CI 0.05–0.69 in the <12-months-olds, 2018: OR 0.05, 95 %CI 0.00–0.44, 2019: OR 0.41, 95 %CI 0.10–1.61 in the 12–23-months-olds). The prevalence of OME associated with non-VT pneumococcus increased in the 12–23-month-olds in 2017 (OR 3.09, 95 %CI 1.47–7.45) and returned to the pre-PCV level of prevalence in 2018 and 2019 (OR 0.94, 95 %CI 0.40–2.43 and 1.40, 95 %CI 0.63–3.49). ConclusionPCV10 introduction was associated with a reduction of OME prevalence in infants but not in older children.

The comparison of exacerbation and pneumonia before and after conjugated pneumococcal vaccination in patients with chronic obstructive pulmonary disease, and the effect of inhaled corticosteroid use on results.

Pneumococcal infections and exacerbations are important causes of mortality and morbidity in chronic obstructive pulmonary disease (COPD). The use of inhaled corticosteroids and pneumococcal vaccination are suggested for the control of the disease progression and exacerbations. The aim of this study is to assess the effect of pneumococcal conjugate vaccine on pneumonia and exacerbation in COPD patients using inhaled corticosteroids (ICSs). The secondary aim is to analyze the effect of ICS use and different ICS types, if administered, on exacerbation and pneumonia incidence in the study population. Medical records of 108 adult patients with COPD who were vaccinated with the pneumococcal conjugate vaccine (PCV13) were retrospectively evaluated. The number of acute exacerbations and pneumonia within one year before and after vaccination were evaluated in all included COPD patients. The comparison analysis was also performed based on the ICS types. There were statistically significant differences between the mean numbers of pneumonia and exacerbations before and after vaccination (p<0.05). There were no significant differences in the mean pneumonia attacks and acute exacerbations between patients using ICS and not using ICS (p> 0.05). This study revealed that PCV13 provides a significant decrease in both exacerbation and pneumonia episodes in COPD patients. On the other hand, the use of ICSs and the types of ICSs were not found to have adverse effects on pneumonia and acute exacerbations in vaccinated COPD patients.

Effect of childhood vaccination and antibiotic use on pneumococcal populations and genome-wide associations with disease among children in Nepal: an observational study

SummaryBackgroundPneumococcal disease is a leading cause of bacterial pneumonia and invasive bacterial disease among children globally. The reason some strains of pneumococci are more likely to cause disease, and how interventions such as vaccines and antibiotics affect pneumococcal strains is poorly understood. We aimed to identify genetic regions under selective pressure and those associated with disease through the analysis of pneumococcal whole-genome sequences.MethodsWhole-genome sequencing was performed on pneumococcal isolates collected between January, 2005, and May, 2018, in Kathmandu, Nepal, which included programmatic ten-valent pneumococcal conjugate vaccine (PCV10) introduction in 2015. Isolates were from three distinct cohorts: nasopharyngeal swabs of healthy community-based children, nasopharyngeal swabs of children admitted to hospital with pneumonia, and sterile-site cultures from children admitted to hospital. Across these cohorts we examined serotype distribution, antibiotic resistance, strain distribution, and regions of recombination to determine genes that were undergoing diversifying selection. Genome-wide association studies comparing pneumonia and sterile-site isolates with healthy carriage were used to determine novel variants associated with disease.FindingsAfter programmatic introduction of PCV10, there was a decline in vaccine covered serotypes; however, strains that had expressed these serotypes continued to exist in the post-PCV population. We identified GPSC9 to be a strain of concern due to its high prevalence in disease, multidrug resistance, and ability to switch to an unencapsulated phenotype via insertion of virulence factor pspC into the cps locus. Antibiotic resistance loci to co-trimoxazole were found to be prevalent (pre-PCV10 78% vs post-PCV10 81%; p=0·27) and increasingly prevalent to penicillin (pre-PCV10 15% vs post-PCV10 32%; p<0·0001). Regions with multiple recombinations were identified spanning the surface protein virulence factors pspA and pspC and antibiotic targets pbpX, folA, folC, folE, and folP. Furthermore, we identified variants in lacE2 to be strongly associated with isolates from children with pneumonia and PRIP to be strongly associated with isolates from sterile sites.InterpretationOur work highlights the effect of pneumococcal conjugate vaccines, antibiotics, and host–pathogen interaction in pneumococcal variation, and the pathogen's capability of adapting to these factors at both population-wide and strain-specific levels. Ongoing surveillance of disease-associated strains and further investigation of lacE2 and PRIP as serotype-independent targets for therapeutic interventions is required.FundingGavi, The Vaccine Alliance; WHO; Bill & Melinda Gates Foundation; Wellcome Sanger Institute; and US Centers for Disease Control and Prevention.

W076 The effects of pneumococcal conjugate vaccine (PCV13) on Russian children: A single center experience

W076 The effects of pneumococcal conjugate vaccine (PCV13) on Russian children: A single center experience

Effectiveness of Pneumococcal Conjugate Vaccination Against Virus-Associated Lower Respiratory Tract Infection Among Adults: A Case-Control Study.

BackgroundInteractions of Streptococcus pneumoniae with viruses feature in the pathogenesis of numerous respiratory illnesses.MethodsWe undertook a case-control study among adults at Kaiser Permanente Southern California between 2015 and 2019. Case patients had diagnoses of lower respiratory tract infection (LRTI; including pneumonia or nonpneumonia LRTI diagnoses), with viral infections detected by multiplex polymerase chain reaction testing. Controls without LRTI diagnoses were matched to case patients by demographic and clinical attributes. We measured vaccine effectiveness (VE) for 13-valent (PCV13) against virus-associated LRTI by determining the adjusted odds ratio for PCV13 receipt, comparing case patients and controls.ResultsPrimary analyses included 13 856 case patients with virus-associated LRTI and 227 887 matched controls. Receipt of PCV13 was associated with a VE of 24.9% (95% confidence interval, 18.4%–30.9%) against virus-associated pneumonia and 21.5% (10.9%–30.9%) against other (nonpneumonia) virus-associated LRTIs. We estimated VEs of 26.8% (95% confidence interval, 19.9%–33.1%) and 18.6% (9.3%–27.0%) against all virus-associated LRTI episodes diagnosed in inpatient and outpatient settings, respectively. We identified statistically significant protection against LRTI episodes associated with influenza A and B viruses, endemic human coronaviruses, parainfluenza viruses, human metapneumovirus, and enteroviruses but not respiratory syncytial virus or adenoviruses.ConclusionsAmong adults, PCV13 conferred moderate protection against virus-associated LRTI. The impacts of pneumococcal conjugate vaccines may be mediated, in part, by effects on polymicrobial interactions between pneumococci and respiratory viruses.

Protective effect of pneumococcal conjugate vaccination on the short-term association between low temperatures and childhood pneumonia hospitalizations: Interrupted time-series and case-crossover analyses in Matlab, Bangladesh

Studies have shown that ambient extreme temperatures (heat and cold) were associated with an increased risk of childhood pneumonia, but the evidence is very limited in low-middle-income countries. It also remains unknown whether pneumococcal conjugate vaccine (PCV) could prevent temperature-related childhood pneumonia. This study collected data on ambient temperature and hospitalizations for childhood pneumonia in Matlab, Bangladesh from 2012 to 2016. Interrupted time series (ITS) analysis was employed to assess the impact of PCV (10-valent) intervention on childhood pneumonia hospitalizations. A time-stratified case-crossover analysis with a conditional logistic regression was performed to examine the association of childhood pneumonia hospitalizations with extreme temperatures and heatwaves before and after PCV10 intervention. Subgroup analyses were conducted to explore the modification effects of seasons, age, gender, and socioeconomic levels on temperature-related childhood pneumonia hospitalizations. We found that after PCV10 intervention, there was a sharp decrease in hospitalizations for childhood pneumonia (relative risk (RR): 0.59, 95% confidence interval (CI): 0.43–0.83). During the study period, heat effects on childhood pneumonia appeared immediately on the current day (odds ratio (OR): 1.28; 95% CI: 1.02–1.60, lag 0), while cold effects appeared 4 weeks later (OR: 1.53, 95% CI: 1.06–2.22, lag 28). Importantly, cold effects decreased significantly after PCV10 (p-value＜0.05), but heat and heatwave effects increased after PCV10 (p-value＜0.05). Particularly, children from families with a middle or low socioeconomic level, boys, and infants were more susceptible to heat-related pneumonia. This study suggests that PCV10 intervention in Bangladesh may help decrease cold-related not heat-related childhood pneumonia.

Evaluating the effectiveness of pneumococcal conjugate vaccine in Taoyuan city on adult population

Abstract Pneumococcus is one of the major threat for senior citizens health worldwide. Pneumococcal Conjugate Vaccines (PCV7, PCV10, and PCV13) were gradually commenced in the national pediatric immunization programme in Taiwan since 2005 and polysaccharide pneumococcal vaccine (PPV23) was granted adult indication since 2015. However, in a most-recent nationwide long-term surveillance, the PCV13 serotypes have shifted to being dominated types in that of &amp;gt; = 65 years-old seniors. This study aims to evaluate the PCV13-introduction effectiveness based on a selected test city. Data of the national health insurance research database (NHIRD) between 2013 and 2018 were retrieved to collect data on yearly medical use of citizen aged 65-66 years and were linked to the death registry database for death-ascertainment. Compared to females, males had more hospitalization due to IPD (RR = 1.37, 95% CI: 1.04-1.79) and due to pneumonia (1.69, 1.34-2.14). The introduction of PCV13 free-vaccination was associated with significant reductions of hospitalization by 40% for IPD (0.6, 0.51-0.71) and 36% for pneumonia (0.64, 0.58-0.7) in females. However, the effects were not significant in both sex combined and in males. As far as mortality is concerned, the introduction of the PCV13 free-vaccination had 33% lower risk of all cause death with IPD claimed within one month of death (0.67, 0.49-0.91) and for pneumonia (0.77, 0.60-0.99). This was also observed in both sex combined (0.82, 0.68-0.98) for IPD, but not for pneumonia, or for both events in males. In conclusion, the policy of PCV13 vaccination for seniors aged 65 years was associated with all-cause mortality with IPD or pneumonia claims one month before death. The evidence was stronger in females than in males. The effectiveness for the associated reduced hospitalization has been demonstrated in females. Further analysis with individual vaccination history and extended years is needed. Funding: The current study was funded by Pfizer Limited (Taiwan). Key messages The pneumococcal serotype shift has been found in elderly from PPV-23 vaccine-type to PCV vaccine-type and hence the preparedness of PCV13-introduction for elderly immunization programme is necessary. The findings of this pilot study included the effectiveness of PCV13-introduction in seniors aged 65 years and some implications to subgroup analyses needed for preparing a nationwide implementation.

Antimicrobial resistance in paediatric Streptococcus pneumoniae isolates amid global implementation of pneumococcal conjugate vaccines: a systematic review and meta-regression analysis

SummaryBackgroundPneumococcal diseases are a leading cause of morbidity and mortality among children globally, and the burden of these diseases might be worsened by antimicrobial resistance. To understand the effect of pneumococcal conjugate vaccine (PCV) deployment on antimicrobial resistance in pneumococci, we assessed the susceptibility of paediatric pneumococcal isolates to various antimicrobial drugs before and after PCV implementation.MethodsWe did a systematic review of studies reporting antimicrobial susceptibility profiles of paediatric pneumococcal isolates between 2000 and 2020 using PubMed and the Antimicrobial Testing Leadership and Surveillance database (ATLAS; Pfizer). Population-based studies of invasive pneumococcal disease or nasopharyngeal colonisation were eligible for inclusion. As primary outcome measures, we extracted the proportions of isolates that were non-susceptible or resistant to penicillin, macrolides, sulfamethoxazole–trimethoprim, third-generation cephalosporins, and tetracycline from each study. Where available, we also extracted data on pneumococcal serotypes. We estimated changes in the proportion of isolates with reduced susceptibility or resistance to each antibiotic class using random-effects meta-regression models, adjusting for study-level and region-level heterogeneity, as well as secular trends, invasive or colonising isolate source, and countries' per-capita gross domestic product.FindingsFrom 4910 studies screened for inclusion, we extracted data from 559 studies on 312 783 paediatric isolates. Susceptibility of isolates varied substantially across regions both before and after implementation of any PCV product. On average across all regions, we estimated significant absolute reductions in the proportions of pneumococci showing non-susceptibility to penicillin (11·5%, 95% CI 8·6–14·4), sulfamethoxazole–trimethoprim (9·7%, 4·3–15·2), and third-generation cephalosporins (7·5%, 3·1–11·9), over the 10 years after implementation of any PCV product, and absolute reductions in the proportions of pneumococci resistant to penicillin (7·3%, 5·3–9·4), sulfamethoxazole–trimethoprim (16·0%, 11·0–21·2), third-generation cephalosporins (4·5%, 0·3–8·7), macrolides (3·6%, 0·7–6·6) and tetracycline (2·0%, 0·3–3·7). We did not find evidence of changes in the proportion of isolates non-susceptible to macrolides or tetracycline after PCV implementation. Observed changes in penicillin non-susceptibility were driven, in part, by replacement of vaccine-targeted serotypes with non-vaccine serotypes that were less likely to be non-susceptible.InterpretationImplementation of PCVs has reduced the proportion of circulating pneumococci resistant to first-line antibiotic treatments for pneumonia. This effect merits consideration in assessments of vaccine impact and investments in coverage improvements.FundingBill & Melinda Gates Foundation.

Indirect effects of 13-valent pneumococcal conjugate vaccine on pneumococcal carriage in children hospitalised with acute respiratory infection despite heterogeneous vaccine coverage: an observational study in Lao People’s Democratic Republic

IntroductionEmpiric data on indirect (herd) effects of pneumococcal conjugate vaccines (PCVs) in settings with low or heterogeneous PCV coverage are limited. The indirect effects of PCV, which benefits both vaccinated...

Effect of pneumococcal conjugate vaccination on radiological findings in infants hospitalized with community acquired pneumonia in northern India

Background: The burden of community acquired pneumonia (CAP) in infants is high in India and Streptococcus pneumoniae is stated to be an common etiological agent for it. Hence Pneumococcal Conjugate Vaccination (PCV) has been introduced in India since 2017 in a phased manner. The objective of this study was the effect of PCV on radiological findings of chest in infants hospitalized with WHO-defined CAP. Methods and materials: This prospective hospital-based pneumonia surveillance is ongoing since 2015-2016 in Lucknow and Etawah districts of Uttar Pradesh and Patna and Darbhanga districts of Bihar, India, after institutional ethical approvals. Recruitments were done from a network of hospitals formed especially for the project. Infants (2-11 months) hospitalized with WHO-defined CAP from index districts with < 14 days of symptoms were recruited after parental consent. Clinical data was abstracted. Chest X-rays (CXRs) were digitalized and interpreted by a panel of three independent blinded radiologists. Results: From May 2017 to October 2018, 282 (22.7% females) infants with PCV vaccination (cases) and 570 (29.8% females) without PCV vaccination (controls) with interpretable CXRs were analyzed. Primary end point pneumonia (PEP) + other infiltrate (OI) were found in 43 (15.2%) cases and 140 (24.7%) controls (p = 0.001); OI in 30 (10.6%) cases and 69 (12.1%) controls (p = 0.5) and normal CXR in 209 (74.1%) cases and 361(63.3%) controls (p = 0.001). There was one death among cases whose CXR showed OI. There were 22 deaths among controls whose CXRs showed PEP + OI in 12 (54.6%); OI in 3 (13.6%) and normal 7 (31.8%). Crude odds ratio for death among cases was 0.088 (95%: CI 0.012-0.66). Conclusion: Among hospitalized patients of CAP, radiological findings differ by PCV vaccination status in infants.

For children younger than one year of age, what are the effects of pneumococcal conjugate vaccines?

For children younger than one year of age, what are the effects of pneumococcal conjugate vaccines?

The direct effect of pneumococcal conjugate vaccines on invasive pneumococcal disease in children in the Latin American and Caribbean region (SIREVA 2006–17): a multicentre, retrospective observational study

Streptococcus pneumoniae isolated from patients with invasive pneumococcal disease has been subjected to laboratory-based surveillance in Latin American and Caribbean countries since 1993. Invasive pneumococcal diseases remain a major cause of death and disability worldwide, particularly in children. We therefore aimed to assess the direct effect of pneumococcal conjugate vaccines (PCVs) on the distribution of pneumococcal serotypes causing invasive pneumococcal disease in children younger than 5 years before and after PCV introduction. We did a multicentre, retrospective observational study in eight countries that had introduced PCV (ie, PCV countries) in the Latin American and Caribbean region: Argentina, Brazil, Chile, Colombia, Dominican Republic, Mexico, Paraguay, and Uruguay. Cuba and Venezuela were also included as non-PCV countries. Isolate data for Streptococcus pneumoniae were obtained between 2006 and 2017 from children younger than 5 years with an invasive pneumococcal disease from local laboratories or hospitals. Species' confirmation and capsular serotyping were done by the respective national reference laboratories. Databases from the Sistema Regional de Vacunas (SIREVA) participating countries were managed and cleaned in a unified database using Microsoft Excel 2016 and the program R (version 3.6.1). Analysis involved percentage change in vaccine serotypes between pre-PCV and post-PCV periods and the annual reporting rate of invasive pneumococcal diseases per 100 000 children younger than 5 years, which was used as a population reference to calculate percentage vaccine type reduction. Between 2006 and 2017, 12 269 isolates of invasive pneumococcal disease were collected from children younger than 5 years in the ten Latin American and Caribbean countries. The ten serotypes included in ten-valent pneumococcal conjugate vaccine (PCV10) decreased significantly (p<0·0001) after any PCV introduction, except for the Dominican Republic. The percentage change for the ten vaccine serotypes in PCV10 countries was -91·6% in Brazil (530 [72·9%] of 727 before, 27 [6·1%] of 441 after); -85·0% in Chile (613 [72·6%] of 844 before, 44 [10·9%] of 404] after); -84·7% in Colombia (231 [63·1%] of 366 before, 34 [9·7%] of 352 after); and -73·8% in Paraguay (127 [77·0%] of 165 before, 22 [20·2%] of 109 after). In the 13-valent pneumococcal conjugate vaccine (PCV13) countries, the percentage change for the 13 vaccine serotypes was -59·6% in Argentina (853 [85·0%] of 1003 before, 149 [34·3%] of 434 after); -16·5% in the Dominican Republic (95 [80·5%] of 118 before, 39 [67·2%] of 58 after); -43·7% in Mexico (202 [73·2%] of 276 before, 63 [41·2%] of 153 after); and -45·9% in Uruguay (138 [80·7%] of 171 before, 38 [43·7%] of 87 after). Annual reporting rates showed a reduction from -82·5% (6·21 before vs 1·09 after per 100 000, 95% CI -61·6 to -92·0) to -94·7% (1·15 vs 0·06 per 100 000, -89·7 to -97·3) for PCV10 countries, and -58·8% (2·98 vs 1·23 per 100 000, -21·4 to -78·4) to -82·9% (7·80 vs 1·33 per 100 000, -76·9 to -87·4) for PCV13 countries. An increase in the amount of non-vaccine types was observed in the eight countries after PCV introduction together with an increase in their percentage in relation to total invasive strains in the post-PCV period. SIREVA laboratory surveillance was able to confirm the effect of PCV vaccine on serotypes causing invasive pneumococcal disease in the eight PCV countries. Improved monitoring of the effect and trends in vaccine type as well as in non-vaccine type isolates is needed, as this information will be relevant for future decisions associated with new PCVs. None. For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Direct effects of pneumococcal conjugate vaccines among children in Latin America and the Caribbean

In Latin America and the Caribbean, more than 70% of the 52 countries and territories have introduced pneumococcal conjugate vaccines (PCVs) into their national immunisation programmes for infants. More than 73 million children live in the region, and, as of 2018, about 82% had received at least three doses of PCV.1 Many reports have described the benefits of PCVs in North America,2,3 with recent evidence showing these findings in the Latin American and Caribbean countries.4,5 In The Lancet Infectious Diseases, Clara Inés Agudelo and colleagues' observational study6 reports data from the Sistema Regional de Vacunas (SIREVA) network.

Pediatric parapneumonic effusion before and after national pneumococcal vaccination programs in Taiwan

Reports on the effectiveness of pneumococcal conjugate vaccines (PCVs) on pediatric parapneumonic effusion are limited. We report the changes in cases and etiologies of pediatric parapneumonic effusion in a children's hospital before and after national PCV13 vaccination programs. We screened medical records of children 0-18 years admitted to the National Taiwan University Hospital with diagnoses of lobar pneumonia and parapneumonic effusion between 2008 and 2017. Patients with effusion analyses were included. Results of blood, pleural fluid, and respiratory specimens surveyed as standard care were analyzed. Diagnostic testing revealed at least a pathogen in 85% of 202 children with lobar pneumonia and parapneumonic effusion. After national PCV13 immunization, pneumococcal empyema decreased by 72% among 2- to 5-year olds. Mycoplasma pneumoniae was the second most common etiology. There were marked differences in effusion characteristics, metabolic, and respiratory parameters between children infected with pneumococcus and M. pneumoniae. The effectiveness of the national PCV13 immunization programs on pneumococcal empyema was evident and remained substantial after 4 years in Taiwan. Continuous surveillance is important to monitor the emergence of other pathogens including non-PCV serotypes and M. pneumoniae.