Conjugate Vaccine Implementation Research Articles

MOST COMMON PATHOGENS OF OTITIS MEDIA IN PEDIATRICS AND THEIR RESISTANCE TO ANTIMICROBIAL AGENTS

Acute otitis media (AOM) stands as a prevalent child­hood illness, frequently necessitating antibiotic treatment. Its burden is significant, affecting about 80% of children under 3 years old, with approximately 40% experiencing recurrent episodes by age 3. In a study spanning Euro­pean countries, including Lithuania, middle ear otitis occurred at a rate of 160.7 cases per 100,000 children per year. Post-pneumococcal conjugate vaccine (PCV) implementation, causative agents shifted towards non-vaccine pneumococcal types and Haemophilus influen­zae. Antibiotic prescription rates, as noted from surveys of European pediatricians, range up to 78% for otitis media with effusion (OME). Commonly prescribed me­dications include amoxicillin (88.5%), amoxicillin-cla­vulanate (7.8%), cephalosporins (3.4%), and macrolides (0.3%). Despite similar antibiotic prescription frequen­cies in Eastern Europe and the Baltic, prescription practi­ces differ, influenced by active otitis monitoring. In this review article, we care to provide up to date cri­tical review of the literature on AOM prevalence, most common pathogens and antimicrobial resistance. Conclusions and recommendations. The most common pathogens of acute otitis media are Streptococcus pneu­moniae and Haemophilus influenzae, with S. pneumoniae often showing resistance to penicillin and erythromycin, while H. influenzae tends to be resistant primarily to ampicillin and amoxicillin when combined with clavu­lanic acid; however, due to increased PCV vaccination, H. influenzae is becoming more prevalent, especially among patients unresponsive to first-line treatment with amoxicillin, often due to β-lactamase-producing strains.

Incidence of typhoid fever in Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria (the Severe Typhoid in Africa programme): a population-based study

Typhoid Fever remains a major cause of morbidity and mortality in low-income settings. The Severe Typhoid in Africa programme was designed to address regional gaps in typhoid burden data and identify populations eligible for interventions using novel typhoid conjugate vaccines. A hybrid design, hospital-based prospective surveillance with population-based health-care utilisation surveys, was implemented in six countries in sub-Saharan Africa. Patients presenting with fever (≥37·5°C axillary or ≥38·0°C tympanic) or reporting fever for three consecutive days within the previous 7 days were invited to participate. Typhoid fever was ascertained by culture of blood collected upon enrolment. Disease incidence at the population level was estimated using a Bayesian mixture model. 27 866 (33·8%) of 82 491 participants who met inclusion criteria were recruited. Blood cultures were performed for 27 544 (98·8%) of enrolled participants. Clinically significant organisms were detected in 2136 (7·7%) of these cultures, and 346 (16·2%) Salmonella enterica serovar Typhi were isolated. The overall adjusted incidence per 100 000 person-years of observation was highest in Kavuaya and Nkandu 1, Democratic Republic of the Congo (315, 95% credible interval 254-390). Overall, 46 (16·4%) of 280 tested isolates showed ciprofloxacin non-susceptibility. High disease incidence (ie, >100 per 100 000 person-years of observation) recorded in four countries, the prevalence of typhoid hospitalisations and complicated disease, and the threat of resistant typhoid strains strengthen the need for rapid dispatch and implementation of effective typhoid conjugate vaccines along with measures designed to improve clean water, sanitation, and hygiene practices. The Bill & Melinda Gates Foundation.

Fusion of PspA to detoxified pneumolysin enhances pneumococcal vaccine coverage

Despite the implementation of conjugate vaccines in several countries, S. pneumoniae continues to pose a great burden worldwide, causing around 1 million annual deaths. Pneumococcal proteins have long been investigated as serotype-independent vaccines against this pathogen, with promising results. However, it is a consensus that one antigen alone will not be sufficient to provide long-term protection with wide coverage. Amongst the most well studied pneumococcal proteins are PspA and pneumolysin (Ply), two major virulence factors required by the bacterium for successful invasion of host tissues. PspA is highly immunogenic and protective, but it is structurally variable; pneumolysin is conserved among different pneumococci, but it is toxic to the host. To overcome these limitations, N-terminal PspA fragments have been genetically fused to non-toxic pneumolysin derivatives (PlD) to create PspA_PlD chimeras. Mouse immunization with these fusions confers protection against pneumococcal strains expressing heterologous PspAs, which correlates with antibody-induced complement C3 deposition on the surface of multiple pneumococcal strains. Analysis of mutant strains lacking PspA or Pneumolysin shows that both proteins contribute to the antibody-mediated enhancement in complement deposition induced by the fusion. These results expand previous data evaluating PspA_PlD and demonstrate that the fusion combines the protective traits of both proteins, inducing antibodies that efficiently promote complement deposition on multiple strains and cross-protection.

Effect of 13-valent pneumococcal conjugate vaccine on experimental carriage of Streptococcus pneumoniae serotype 6B in Blantyre, Malawi: a randomised controlled trial and controlled human infection study

The effect of childhood pneumococcal conjugate vaccine implementation in Malawi is threatened by absence of herd effect. There is persistent vaccine-type pneumococcal carriage in both vaccinated children and the wider community. We aimed to use a human infection study to measure 13-valent pneumococcal conjugate vaccine (PCV13) efficacy against pneumococcal carriage. We did a double-blind, parallel-arm, randomised controlled trial investigating the efficacy of PCV13 or placebo against experimental pneumococcal carriage of Streptococcus pneumoniae serotype 6B (strain BHN418) among healthy adults (aged 18-40 years) from Blantyre, Malawi. We randomly assigned participants (1:1) to receive PCV13 or placebo. PCV13 and placebo doses were prepared by an unmasked pharmacist to maintain research team and participant masking with identification only by a randomisation identification number and barcode. 4 weeks after receiving either PCV13 or placebo, participants were challenged with 20 000 colony forming units (CFUs) per naris, 80 000 CFUs per naris, or 160 000 CFUs per naris by intranasal inoculation. The primary endpoint was experimental pneumococcal carriage, established by culture of nasal wash at 2, 7, and 14 days. Vaccine efficacy was estimated per protocol by means of a log-binomial model adjusting for inoculation dose. The trial is registered with the Pan African Clinical Trials Registry, PACTR202008503507113, and is now closed. Recruitment commenced on April 27, 2021 and the final visit was completed on Sept 12, 2022. 204 participants completed the study protocol (98 PCV13, 106 placebo). There were lower carriage rates in the vaccine group at all three inoculation doses (0 of 21 vs two [11%] of 19 at 20 000 CFUs per naris; six [18%] of 33 vs 12 [29%] of 41 at 80 000 CFUs per naris, and four [9%] of 44 vs 16 [35%] of 46 at 160 000 CFUs per naris). The overall carriage rate was lower in the vaccine group compared with the placebo group (ten [10%] of 98 vs 30 [28%] of 106; Fisher's p value=0·0013) and the vaccine efficacy against carriage was estimated at 62·4% (95% CI 27·7-80·4). There were no severe adverse events related to vaccination or inoculation of pneumococci. This is, to our knowledge, the first human challenge study to test the efficacy of a pneumococcal vaccine against pneumococcal carriage in Africa, which can now be used to establish vaccine-induced correlates of protection and compare alternative strategies to prevent pneumococcal carriage. This powerful tool could lead to new means to enhance reduction in pneumococcal carriage after vaccination. Wellcome Trust.

Prevention of pneumococcal diseases: the challenge remains

Streptococcus pneumoniae (pneumococcus) is a leading cause of pneumonia that kills almost a million children worldwide annually, mostly in African and Asian countries.1 By 2015, 129 countries have introduced pneumococcal conjugate vaccines (PCVs) that have substantially reduced child morbidity and mortality.2 However, post-vaccine surveillance has shown the emergence of diseases caused by non-vaccine serotypes as well as serotype replacement in nasopharyngeal colonisation.3 Although an impact of vaccination on invasive pneumococcal disease has been observed in young children (particularly those younger than 2 years, even after many years of pneumococcal conjugate vaccine implementation) the emergence of non-vaccine serotypes with antibiotic resistance has become a new global threat to the control and prevention of pneumococcal diseases.

Epidemiology of pediatric parapneumonic pleural effusion during 13-valent pneumococcal conjugate vaccine implementation

IntroductionThe reported incidence of parapneumonic pleural effusion, including empyema, has shown fluctuations in the last decades. It has been related to the implementation of different types of conjugate pneumococcal vaccines. MethodsWe have retrospectively reviewed data from all 10 public hospitals in Alicante Province (Spain) covering a population of 279,000 children under 15 years of age, between 2010 and 2018. Effusions less than 10 mm (PE−) and those of 10 mm or more (PE+) were separated. ResultsA total of 366 episodes of parapneumonic pleural effusion have been analyzed, 178 PE− (48.6%) and 188 PE+ (51.4%), with a median age of 4 years (interquartile range: 2–7 years) and marked seasonality with the maximum in winter and the minimum in summer. A culture proven bacterial agent was identified in 34 patients (9.3%), mainly Streptococcus pneumoniae (24 patients) followed by Streptococcus pyogenes (7 patients). The most frequent S. pneumoniae serotype was 19A (6 patients) and 3 vaccine failures were observed. The mean annual incidence rate was 14.3 cases per 100,000 children under 15 years of age (7.0 for PE− and 7.3 for PE+). No significant changes were observed in incidence over time, but noticeable differences in incidence were observed in different health departments. ConclusionsWe have not found temporal variations in incidence of parapneumonic effusion despite the implementation of the 13-valent pneumococcal conjugate vaccine. The unexplained disparity in incidence between close departments is noteworthy.

Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Following Implementation of the 13-Valent Pneumococcal Conjugate Vaccine in France

Acute chest syndrome (ACS) is one of the leading acute severe complications of sickle-cell disease (SCD). Although Streptococcus pneumoniae (S pneumoniae) is highly prevalent in children with SCD, its precise role in ACS is unclear. The efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) implementation on ACS is still unknown. To assess the association of PCV13 implementation in the general pediatric population with the incidence of ACS in children with SCD. This cohort study used an interrupted time-series analysis of patient records from a national hospital-based French surveillance system. All children younger than 18 years with SCD (based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision definition) hospitalized in France between January 2007 and December 2019 were included. PCV13 implementation. Monthly incidence of ACS per 1000 children with SCD over time as analyzed by segmented linear regression with autoregressive error; monthly incidence of hospitalization for vaso-occlusive crisis, asthma crisis, and acute pyelonephritis per 1000 children with SCD over the same period as the control outcomes. Among the 107 694 hospitalizations of children with SCD, 4007 episodes of ACS were included (median [IQR] age, 8 [4-12] years; 2228 [55.6%] boys). PCV13 implementation in 2010 was followed by a significant decrease in the incidence of ACS (-0.9% per month; 95% CI, -1.4% to -0.4%; P < .001), with an estimated cumulative change of -41.8% (95% CI, -70.8% to -12.7%) by 2019. Sensitivity analyses yielded the same results, including the incidence of ACS adjusted for that of vaso-occlusive crisis over time. The results were similar among different age groups. By contrast, no change was found for the 3 control outcomes over the study period. PCV13 implementation was associated with an important reduction in the incidence of ACS in children with SCD. This vaccine benefit provides new evidence of the key role of S pneumoniae in ACS and should be considered when estimating outcomes associated with current PCVs and the potential benefit of next-generation PCVs in children.

Clinical Presentations and Outcomes of Children in Canada With Recurrent Invasive Pneumococcal Disease From the IMPACT Surveillance Network.

Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate. This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0-16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada. The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers. The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children.

Vaccine Impact and Effectiveness of Meningococcal Serogroup ACWY Conjugate Vaccine Implementation in the Netherlands: A Nationwide Surveillance Study.

BackgroundIn response to the recent serogroup W invasive meningococcal disease (IMD-W) epidemic in the Netherlands, meningococcal serogroup C (MenC) conjugate vaccination for children aged 14 months was replaced with a MenACWY conjugate vaccination, and a mass campaign targeting individuals aged 14–18 years was executed. We investigated the impact of MenACWY vaccination implementation in 2018–2020 on incidence rates and estimated vaccine effectiveness (VE).MethodsWe extracted IMD cases diagnosed between July 2014 and December 2020 from the national surveillance system. We calculated age group–specific incidence rate ratios by comparing incidence rates before (July 2017–March 2018) and after (July 2019–March 2020) MenACWY vaccination implementation. We estimated VE in vaccine-eligible cases using the screening method.ResultsOverall, the IMD-W incidence rate declined by 61% (95% confidence interval [CI], 40 to 74). It declined by 82% (95% CI, 18 to 96) in the vaccine-eligible age group (individuals aged 15–36 months and 14–18 years) and by 57% (95% CI, 34 to 72) in vaccine-noneligible age groups. VE was 92% (95% CI, –20 to 99.5) in vaccine-eligible toddlers (aged 15–36 months). No IMD-W cases were reported in vaccine-eligible teenagers after the campaign.ConclusionsThe MenACWY vaccination program was effective in preventing IMD-W in the target population. The IMD-W incidence reduction in vaccine-noneligible age groups may be caused by indirect effects of the vaccination program. However, disentangling natural fluctuation from vaccine effect was not possible. Our findings encourage the use of toddler and teenager MenACWY vaccination in national immunization programs.

Decline in pneumococcal nasopharyngeal carriage in children 6–23 months with respiratory illnesses following pneumococcal conjugate vaccine implementation

BackgroundFollowing pneumococcal conjugate vaccines (PCVs) implementation, worldwide, pneumococcal carriage rates remained stable, indicating full replacement of vaccine-serotypes (VT) with non-VT. However, data are scarce regarding PCV impact on pneumococcal carriage rates in healthy vs. sick children. We assessed pneumococcal carriage rates dynamics in healthy and sick children 6–23 months, following PCV introduction. MethodsThis is a prospective, population-based surveillance conducted during the years 2009–2017, in southern Israel. Three groups were defined as follows: Children without respiratory infection signs (the healthy/non-respiratory group); Children who had a chest radiography at the hospital (the Hosp-CXR group); and children with community-acquired alveolar pneumonia (CAAP).Rate ratios (RRs; 95% CI) were calculated, comparing between late-13-valent PCV (PCV13) period (2016–2017) and early-PCV period (2009–2010). Rate ratios were adjusted for antibiotic administration, seasonality and ethnicity, and separate calculations were performed for 6–11 and 12–23 month old children. ResultsOverall, 51% of 8627 nasopharyngeal cultures were positive.In 2009–2010 (early-PCV period), the overall carriage rate was 55%; serotypes included in the PCV13 carriage rates were 28%, 31% and 38% in the healthy/non-respiratory, Hosp-CXR, and CAAP groups, respectively.Overall carriage rates in healthy/non-respiratory episodes were stable (~54%) when comparing between 2016 and 17 and 2009–10 (RR = 0.98; 0.84–1.15). In contrast, rates significantly declined for Hosp-CXR (RR = 0.78; 0.63–0.98) and CAAP (RR = 0.65; 0.47–0.89). These trends were driven by ~ 80% VT reductions, coupled with non-VT increase. ConclusionsFollowing 7-valent PCV/ PCV13 introduction, pneumococcal carriage rates declined in respiratory diseases, but not in healthy children and children without respiratory infections. These trends suggest that a reduction in pneumococcal carriage rates during respiratory infections indicates a decline in respiratory infections caused by VT, while carriage rates in non-respiratory cases reflect non-VT predominance, that have low disease potential for respiratory disease.

Impact of pneumococcal conjugate vaccines on healthcare utilization and direct costs for otitis media in children ≤2 years of age in two Swedish regions

ABSTRACT In Sweden, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2009 and replaced by the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) or the 13-valent PCV (PCV13) from late 2009. We assessed the impact of PCVs on rates of antibiotic prescribing, tympanostomy tube placement (TTP), and healthcare resource utilization and direct costs of physician-diagnosed otitis media/acute otitis media (OM) in children ≤2 years of age living in Skåne (PCV7 then PHiD-CV) or Västra Götalandsregionen (VGR; PCV7 then PCV13). Retrospective cohort study using linked patient-level data from national and regional (Skåne and VGR) healthcare databases in Sweden from July 1, 2005, to December 31, 2013 (NCT02742753). Descriptive time-series analyses showed antibiotic prescriptions and TTP incidence declined after PHiD-CV/PCV13 introduction versus the pre-PCV period. The annualized mean frequencies of antibiotic use, primary care visits, outpatient visits, TTP and myringotomy procedures all decreased after PHiD-CV/PCV13 compared with pre-PCV cohorts. Annualized mean total OM-associated healthcare costs decreased in the PCV7 versus pre-PCV cohorts by 20.0% in Skåne and 10.2% in VGR, and further declined in the PHiD-CV and PCV13 cohorts (20.7% and 15.3%, respectively, relative to the PCV7 cohort), although the duration of PCV7 use differed between regions. Decreases in adjusted annualized cost ratios between cohorts per child susceptible to OM were statistically significant after PCV7 introduction and again with either PHiD-CV or PCV13 introduction in both regions. Following sequential PCV introduction, OM-related healthcare utilization and associated costs decreased in the study regions in Sweden. PLAIN LANGUAGE SUMMARY What is the context? Otitis media is one of the most frequent reasons for healthcare visits and antibiotic use among young children. Although it is considered as a mild illness, the overall economic burden is substantial due to its high frequency. Otitis media can be caused by different bacteria including Streptococcus pneumoniae, which is also responsible for pneumonia and meningitis. Pneumococcal conjugate vaccines Prevenar (Pfizer Inc.), Synflorix (GSK), and Prevenar 13 (Pfizer Inc.) protect against pneumococcal diseases and reduce its occurrence. However, it is not known how the routine use of these vaccines may affect otitis media-related healthcare resources and costs. What is new? In this study, we assessed trends in rates of healthcare utilization and associated costs due to otitis media in young children before (2005–2008) and after (2009–2013) use of pneumococcal conjugate vaccines. The study was conducted in two Swedish regions; one used Prevenar then Synflorix, while the other used Prevenar then Prevenar 13. We found that compared to the period before pneumococcal conjugate vaccine implementation, the post-pneumococcal conjugate vaccine period was associated with: A decrease in otitis media-related antibiotic prescriptions and surgical procedures in both regions. A decrease in the annual frequency of otitis media related antibiotic use, primary care and outpatient visits, and surgical procedures. A significant reduction in otitis media-related healthcare costs in both regions. What is the impact on current thinking? The use of pneumococcal conjugate vaccines effectively reduces healthcare utilization and resources associated with otitis media. This indirect effect on the reduction of otitis media burden provides further benefit to the implementation of pneumococcal vaccination.

Dynamics of Invasive Pneumococcal Disease in Israel in Children and Adults in the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Era: A Nationwide Prospective Surveillance.

Following 13-valent pneumococcal conjugate vaccine (PCV13) implementation in infants worldwide, overall and vaccine-type invasive pneumococcal disease (IPD) rates declined in children, with variable indirect impact on adults. A population-based, prospective, nationwide active surveillance of IPD in Israel, 2004-2019 (for adults ≥18 years, 2009-2019). The 7-valent PCV (PCV7)/PCV13 were implemented in Israel in July 2009/November 2010, respectively, with >90% uptake in children <2 years. The 23-valent pneumococcal polysaccharide vaccine (PPV-23) uptake among those >65 years was ~75%. For pre-PCV episodes with missing serotype, extrapolations were applied. Overall, PCV13 serotypes (VT13) and non-VT13 (NVT) incidence rate ratios (IRRs) comparing pre-PCV (2004-2008), early-PCV (2009-2011), and late-PCV13 (2016-2019) periods were calculated for different age groups. Overall, 8614 IPD cases were recorded. IPD rates declined by 67% in children <5 and 5-17 years, comparing late-PCV13 versus pre-PCV periods (IRR [95% CI]: .33 [.27-.40] and .33 [.21-.50], respectively). For adults, comparing late-PCV13 with early-PCV periods, rates significantly declined by 53% in those aged 18-44, while rates did not decline significantly in other age groups. VT13 rates significantly declined in all ages, with decline rates ranging between 94% in children <5 years and 60% in adults ≥85 years. NVT rates significantly increased in <5-, 50-64-, and ≥65-year age groups. In the late-PCV13 period, serotypes 3, 14, and 19A remained the predominant VT13, while serotypes 8 and 12F emerged as predominant NVTs. Continuous monitoring of circulating serotypes in all ages demonstrated direct and indirect PCV effects, which are essential for the development of new vaccination strategies.

Pneumococcal Meningitis in Adults: A Prospective Nationwide Cohort Study Over a 20-year Period.

BackgroundThe epidemiology and treatment of pneumococcal meningitis has changed with the implementation of conjugate vaccines and the introduction of adjunctive dexamethasone therapy.MethodsWe analyzed episodes of community-acquired pneumococcal meningitis in adults (≥16 years) in the Netherlands, identified by the National Reference Laboratory for Bacterial Meningitis or treating physician between October 1, 1998, and April 1, 2002, and between January 1, 2006, and July 1, 2018. We studied incidence, pneumococcal serotypes, and clinical features. Predictors for unfavorable outcome (Glasgow Outcome Scale score 1–4) were identified in a multivariable logistic regression model. Two physicians independently categorized causes of death as neurological or systemic.ResultsThere were 1816 episodes in 1783 patients. The incidence of 7- and 10−7-valent pneumococcal conjugate vaccine serotypes decreased (from 0.42 to 0.06, P = .001; from 0.12 to 0.03 episodes per 100 000 population per year, P = .014). Incidence of nonvaccine serotypes increased (from 0.45 to 0.68, P = .005). The use of adjunctive treatment with dexamethasone increased and was administered in 85% of patients in 2018. In-hospital death occurred in 363 episodes (20%) and unfavorable outcome in 772 episodes (43%). Delayed cerebral thrombosis occurred in 29 patients (2%), of whom 15 patients (52%) died. Adjunctive dexamethasone therapy was associated with favorable outcome (adjusted odds ratio 2.27, P < .001), individual pneumococcal serotypes were not.ConclusionImplementation of conjugate vaccines and adjunctive dexamethasone therapy have changed the incidence and outcome of pneumococcal meningitis in adults over the last two decades. Despite recent advances pneumococcal meningitis remains associated with a residual high rate of mortality and morbidity.

A Nationwide Outbreak of Invasive Pneumococcal Disease in Israel Caused by Streptococcus pneumoniae Serotype 2.

Invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae serotype 2 (Sp2) is infrequent. Large-scale outbreaks were not been reported following pneumococcal conjugate vaccine (PCV) implementation. We describe a Sp2 IPD outbreak in Israel, in the PCV13 era, with focus on Sp2 population structure and evolutionary dynamics. The data were derived from a population-based, nationwide active surveillance of IPD since 2009. PCV7/PCV13 vaccines were introduced in July 2009 and November 2010, respectively. Sp2 isolates were tested for antimicrobial susceptibility, multilocus sequence typing, and whole-genome sequencing (WGS) analysis. Overall, 170 Sp2 IPD cases were identified during 2009-2019; Sp2 increased in 2015 and caused 6% of IPD during 2015-2019, a 7-fold increase compared with 2009-2014. The outbreak was caused by a previously unreported molecular type (ST-13578), initially observed in Israel in 2014. This clone caused 88% of Sp2 during 2015-2019. ST-13578 is a single-locus variant of ST-1504, previously reported globally including in Israel. WGS analysis confirmed clonality among the ST-13578 population. Single-nucleotide polymorphism-dense regions support a hypothesis that the ST-13578 outbreak clone evolved from ST-1504 by recombination. All tested strains were penicillin-susceptible (minimum inhibitory concentration <0.06 μg/mL). The ST-13578 clone was identified almost exclusively (99%) in the Jewish population and was mainly distributed in 3 of 7 Israeli districts. The outbreak is still ongoing, although it began declining in 2017. To the best of our knowledge, this is the first widespread Sp2 outbreak since PCV13 introduction worldwide, caused by the emerging ST-13578 clone.

Epidemiology, Nasopharyngeal Carriage, Serotype Prevalence, and Antibiotic Resistance of Streptococcus pneumoniae in Indonesia.

In Indonesia, pneumococcal disease represents a considerable public health concern; however, published data on the epidemiology, nasopharyngeal carriage, serotype prevalence, and antibiotic resistance of Streptococcus pneumoniae in this region are limited. Therefore, this article reviews the available data from a variety of sources and also summarizes pneumococcal conjugate vaccine implementation and recommendations in Indonesia and subsequent impact on pneumococcal disease. Regional pneumococcal vaccination recommendations in Asia were also reviewed. Studies showed that pneumococcal nasopharyngeal carriage prevalence in Indonesia was approximately 43% to 55% in healthy children aged less than 5 years, which varied by age group, region, and year. Serotype analysis of pneumococcal nasopharyngeal carriage isolates in Indonesia revealed that 38% to 60% of isolates would be covered by the 13-valent pneumococcal conjugate vaccine (PCV13). The antimicrobial resistance of pneumococcal disease has increased over time; between 1997 and 2012, resistance to penicillin and sulfamethoxazole increased from 0% to 28% and 9% to 62%, respectively. Inclusion of pneumococcal conjugate vaccines into immunization programs is being implemented gradually. In 2017, Indonesia implemented a regional PCV13 immunization program in Lombok with a 2 + 1 vaccination schedule that was expanded in 2018–2019 to West Nusa Tenggara and Bangka Belitung Provinces; this expansion is predicted to substantially reduce the burden of pneumococcal disease in Indonesia. Overall, the limited data available regarding pneumococcal disease in Indonesia highlight the unmet need for comprehensive disease surveillance studies in this region that can help direct vaccination strategies.

Etiology of Pediatric Meningitis in West Africa Using Molecular Methods in the Era of Conjugate Vaccines against Pneumococcus, Meningococcus, and Haemophilus influenzae Type b.

.Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for N. meningitidis, S. pneumoniae, and H. influenzae used in routine meningitis surveillance. A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and Plasmodium. Overall, Escherichia coli was the most prevalent (4.8%), followed by S. pneumoniae (3.5%) and Plasmodium (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and Plasmodium detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance.

ANTIMICROBIAL SUSCEPTIBILITY OF S. PNEUMONIAE STRAINS ISOLATED FROM CHILDREN WITH NASOPHARYNGEAL CARRIAGE

Streptococcus pneumoniae colonises the nasopharynx of children and could cause life-threatening diseases. As a result of the implementation of conjugate vaccines worldwide the spread of vaccine serotypes has decreased. In Bulgaria PCV10 was introduced in 2010 followed by changes in the invasive clones carrying resistance genes. The aim of our study is to determine the serotype distribution and resistance patterns of isolates from children carriers after vaccination. A total of 834 children were tested for S. pneumoniae and 21% showed positive culture results. All isolates were genotyped with PCR. We found that 85% of the positive samples are from children attending kindergartens and schools. The most frequent serotypes/serogroups were 6C (20%) and 24B/F (11.5%), followed by 3 (8.6%), 11A/D (8%), 35F (6.9%), 19A (6.3%), 23A (6.3%) and 15A/F (6.3%). The susceptibility to β-lactams was high and there were strains showing intermediate susceptibility to benzylpenicillin. This study found 76 (44%) MDR strains non-susceptible to at least 3 antibiotic classes and the most common resistance pattern was erythromycin-clindamycin-tetracycline.

Lower respiratory infections mortality among Brazilians under-five before and after national pneumococcal conjugate vaccine implementation

BackgroundStudies on the impact of pneumococcal conjugate vaccines (PCV) on mortality, especially among preschoolers are scarce. We aimed to assess time trend mortality from lower respiratory infections (LRI), taken as a proxy of pneumonia, from 1990 to 2017. MethodsThis ecological study assessed the mortality rate among Brazilians under-five before and after the national PCV-10 implementation in 2010. Pneumococcal meningitis (PM) and diarrheal diseases (DD) were included as a “positive and negative controls”, respectively. Trend analysis was performed through Global Burden of Disease estimates. Joinpoint regression modeling was used to describe trends in mortality and to identify time points of its statistically significant decreases throughout the study period. ResultsThere was a sustainable reduction in mortality rates for these three diseases, with no relevant changes in the secular trends for LRI and PM after the PCV-10 implementation. For LRI, PM, and DD the higher and statistically significant (p < 0.05) annual percent change reduction occurred between 2000 and 2003, (−8.3%), 1997–2000 (−11.9%), and 1990–1994.(−13.8%), respectively, i.e., several years before the nationwide implementation of PCV-10. Moreover, for LRI the annual percent change (from −5.9 to −8.8) verified from 1990 to 2009, i.e., 20 years before countrywide vaccination, was comparable to that observed during the PCV era, that is, from minus 5.8 to minus 7.8, between 2010 and 2017. ConclusionMortality from LRI, PM, and DD decreased over time, irrespective of national PCV-10 implementation in Brazil. Other factors such as healthcare delivery, socioeconomic status improvement, and health interventions may have impacted this secular trend.

Pneumococcal conjugate vaccines decrease community-acquired alveolar pneumonia with and without pleural effusion in children

Background: Radiographically-proven community-acquired alveolar pneumonia with pleural effusion (PE-CAP) has a less favourable outcome than pneumonia without pleural effusion (NPE-CAP). We assessed PE-CAP and NPE-CAP rate dynamics in children <60 months in southern Israel before and after 7- and 13-valent pneumococcal conjugate vaccine (PCV7/PCV13) implementation (2002–2016).Methods: An ongoing, prospective observational study. Our hospital serves a captive population of ∼75,000 children <60 months, enabling incidence calculation. PCV7/PCV13 were implemented in Israel in July 2009/November 2010, respectively. All chest radiographs (CXRs) were digitalized and analysed according to the WHO Standardization of Interpretation. Annual incidences of PE-CAP and NPE-CAP were calculated, 2002–2016. Incidence-rate ratios (IRRs) comparing PCV13 (2013–2016), PCV7 (2010–2011) and pre-PCV (2002–2008) periods were calculated.Results: Overall, 12,271 CAP episodes were identified; 159 (1.3%) PE-CAP and 12,112 (98.7%) NPE-CAP. In total, 65.8% and 34.2% were children <24 and 24–59 months, respectively; 61.0% and 39.0% were Bedouin and Jewish children, respectively. Following PCV7 introduction, PE-CAP rates declined by 48% (Incidence rate ratios [IRR] = 0.52; 0.26–1.03), while NPE-CAP rates declined by 20% (IRR = 0.80; 0.75–0.86). In the PCV13 period, PE-CAP and NPE-CAP rates further declined, resulting in overall 70% (IRR = 0.30; 0.18–0.50) and 55% (IRR = 0.45; 0.43–0.48) reductions, respectively, comparing the PCV13 and the pre-PCV periods. Similar trends were observed in all subgroups (Bedouin vs. Jewish and age < 24 months vs. 24–59 months).Conclusions: Following PCV7/PCV13 introduction, PE-CAP and NPE-CAP rates substantially declined. However, the rate dynamics were different, with steeper declines observed in PE-CAP rates, possibly deriving from differences in disease aetiology.

Nasopharyngeal Carriage of Invasive Pneumococcal Serotypes During Childhood Community-Acquired Alveolar Pneumonia Is Associated With Specific Clinical Presentation.

Streptococcus pneumoniae (Pnc) serotypes differ in invasive potential. We examined whether community-acquired alveolar pneumonia (CAAP) in children carrying commonly recognized pneumonia invasive pneumococcal serotypes ([PnIST] 1, 5, 7F, 14, and 19A) differs from CAAP in children carrying less invasive serotypes (non-PnIST) or no Pnc (Pnc-neg). Children <5 years, visiting the only regional Pediatric Emergency Room, with radiologically proven CAAP were enrolled. Nasopharyngeal cultures were processed for pneumococcal isolation and serotyping. Clinical and demographic characteristics were recorded. The study was conducted before pneumococcal conjugate vaccine implementation in Israel. A total of 1423 CAAP episodes were recorded: PnIST, 300 (21.1%); non-PnIST, 591 (41.5%); and Pnc-neg, 532 (37.4%). After adjustment for age, ethnicity, seasonality, and previous antibiotics, the following variables were positively associated with PnIST carriage compared with both groups: temperature ≥39°C, peripheral white blood cell count ≥20 000/mm3, C-reactive protein ≥70.0 mg/L, and serum sodium <135 mEq/L. Lower oxygen saturation, viral detection, and comorbidities were negatively associated with Pn-IST carriage (odds ratios, <1.0). Differences between non-PnIST carriers and Pnc-neg groups were smaller or nonsignificant. Young children with CAAP carrying common PnIST had a lower proportion of comorbidities, hypoxemia, and viral detection and had more intense systemic inflammatory response than those carrying non-PnIST or not carrying Pnc.