Introduction Of Conjugate Vaccine Research Articles

Cost of the typhoid conjugate vaccine introduction through an integrated campaign and follow-on routine immunization in Malawi

Cost of the typhoid conjugate vaccine introduction through an integrated campaign and follow-on routine immunization in Malawi

A genome-based survey of invasive pneumococci in Norway over four decades reveals lineage-specific responses to vaccination

BackgroundStreptococcus pneumoniae is a major cause of mortality globally. The introduction of pneumococcal conjugate vaccines (PCVs) has reduced the incidence of the targeted serotypes significantly, but expansion of non-targeted serotypes, serotype replacement, and incomplete vaccine-targeting contribute to pneumococcal disease in the vaccine era. Here, we characterize the changing population genetic landscape of S. pneumoniae in Norway over a 41-year period (1982–2022).MethodsSince 2018, all cases of invasive pneumococcal disease have undergone whole-genome sequencing (WGS) at the Norwegian Institute of Public Health. In order to characterize the changing population over time, historical isolates were re-cultured and sequenced, resulting in a historical WGS dataset. Isolates were assigned to global pneumococcal sequence clusters (GPSCs) using PathogenWatch and assigned to serotypes using in silico (SeroBA) and in vitro methods (Quellung reaction). Temporal phylogenetic analyses were performed on GPSCs of particular interest.ResultsThe availability of WGS data allowed us to study capsular variation at the level of individual lineages. We detect highly divergent fates for different GPSCs following the introduction of PCVs. For two out of eight major GPSCs, we identified multiple instances of serotype switching from vaccine types to non-vaccine types. Dating analyses suggest that most instances of serotype switching predated the introduction of PCVs, but expansion occurred after their introduction. Furthermore, selection for penicillin non-susceptibility was not a driving force for the changing serotype distribution within the GPSCs over time.ConclusionsPCVs have been major shapers of the Norwegian disease-causing pneumococcal population, both at the level of serotype distributions and the underlying lineage dynamics. Overall, the introduction of PCVs has reduced the incidence of invasive disease. However, some GPSCs initially dominated by vaccine types escaped the effect of vaccination through expansion of non-vaccine serotypes. Close monitoring of circulating lineages and serotypes will be key for ensuring optimal vaccination coverage going forward.

Epidemiology of pneumococcal meningitis in sentinel hospital surveillance of Viet Nam, 2015–2018

BackgroundStreptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae (H. influenzae), and Neisseria meningitidis (N. meningitidis) are leading causes of childhood bacterial meningitis and preventable by vaccines. The aim of this hospital-based sentinel surveillance is to describe the epidemiological characteristics of pneumococcal meningitis, including disease burden, and to provide baseline data on pneumococcal serotype distribution to support decision making for pneumococcal conjugate vaccine (PCV) introduction in Vietnam.MethodsSurveillance for probable bacterial meningitis in children 1–59 months of age is conducted in three tertiary level pediatric hospitals: one in Hanoi and two in Ho Chi Minh City. Cerebrospinal fluid (CSF) specimens were collected via lumbar puncture from children with suspected meningitis. Specimens were transferred immediately to the laboratory department of the respective hospital for cytology, biochemistry, and microbiology testing, including culture. PCR testing was conducted on CSF specimens for bacterial detection (S. pneumoniae, H. influenzae, and N. meningitidis) and pneumococcal serotyping.ResultsDuring 2015–2018, a total of 1,803 children with probable bacterial meningitis were detected; 1,780 had CSF specimens available for testing. Of 245 laboratory-confirmed positive cases, the majority were caused by S. pneumoniae (229,93.5%). Of those with S. pneumoniae detected, over 70% were caused by serotypes included in currently available PCV products; serotypes 6 A/6B (27.1%), 14 (19.7%), and 23 F (16.2%) were the most common serotypes. Children with laboratory-confirmed pneumococcal meningitis were more likely to live in Hanoi (p < 0.0001) and children 12–23 months of age were at greater odds (OR = 1.65, 95% CI: 1.11, 2.43; p = 0.006) of having confirmed pneumococcal meningitis compared to children < 12 months of age when compared to those without laboratory-confirmed bacterial meningitis. Additionally, children with confirmed pneumococcal meningitis were more likely to exhibit signs and symptoms consistent with clinical meningitis compared to negative laboratory-confirmed meningitis cases (p < 0.0001) and had a greater odds of death (OR = 6.18, 95% CI: 2.98, 12.86; p < 0.0001).ConclusionsPneumococcal meningitis contributes to a large burden of bacterial meningitis in Vietnamese children. A large proportion are caused by serotypes covered by PCVs currently available. Introduction of PCV into the routine immunization program could reduce the burden of pneumococcal meningitis in Viet Nam.

A Systematic Review and Meta-Analysis of the Efficacy of Antimicrobial Chemoprophylaxis for Recurrent Acute Otitis Media in Children.

Acute otitis media (AOM) is a common childhood infection. Recurrent AOM affects a subset of children, resulting in an adverse impact on quality of life, socioeconomic disadvantage, and risk of long-term sequelae. Antimicrobial chemoprophylaxis is used in some settings but is increasingly controversial due to an awareness of adverse long-term effects and contribution to global antibiotic resistance. A comprehensive literature search was undertaken using Medline (1946-October 2023) and Embase (1974-October 2023). The primary aim was to assess the efficacy of antimicrobial chemoprophylaxis on AOM episodes in children < 18 years of age. Bias and quality assessment was performed. Dichotomous data were analysed using risk ratio with 95% confidence intervals. Meta-analysis was carried out using random-effects models for pooled analysis, independent of heterogeneity. Heterogeneity was assessed using the I2 statistic. The effect of antimicrobial chemoprophylaxis in children with rAOM on the number of individual AOM episodes. assessment of antimicrobial agents and outcomes in children with risk factors. Assessment of qualitative data was performed on 20 studies (n = 2210). No controlled trials were identified post-multivalent pneumococcal conjugate vaccine (PCV) introduction, restricting current generalisability. Quantitative meta-analysis on nine pre-PCV studies (n = 1087) demonstrated antimicrobial chemoprophylaxis reduced any episode of AOM with a risk ratio 0.59 (95% CI 0.45-0.77). Families and clinicians must balance marginal short-medium term benefit (based on pre-PCV data), and the potential for adverse effects to that individual, and the societal risk of antimicrobial resistance with prolonged antibiotic use.

Radiographically confirmed pneumonia in Malawian children and associated pneumococcal carriage after introduction of the 13-valent pneumococcal conjugate vaccine

BackgroundThe 13-valent pneumococcal conjugate vaccine (PCV-13) was introduced in Malawi in 2011 with an expected impact of reducing pneumococcal pneumonia in children. We aimed to describe clinical characteristics and nasopharyngeal (NP) carriage of pneumococcus by serotype in children hospitalized with primary end-point pneumonia (PEP) between 2013 and 19 after the introduction of PCV-13.MethodsWe conducted a secondary analysis of children aged under-5-years hospitalized with acute respiratory illness (ARI) in Malawi. Chest radiographs conducted at admission were read by two independent clinicians according to WHO criteria for PEP, and a third reviewer resolved discordant diagnoses. NP swab specimens were processed and Streptococcus pneumoniae growth was serotyped. Multivariable regression analysis was conducted to assess the association between clinical characteristics, NP serotypes, and PEP.ResultsWe had complete radiographic and NP serotype data for 500 children, of which 54 isolates were vaccine-type (VT) (10.8%), 165 were non-VT (NVT; 33.0%), and 281 had no pneumococcal growth (56.2%). Among these, 176 (35.2%) had PEP on chest x-ray. Among those with PEP, pneumococcal carriage was documented in 43.8% of cases, and VT serotypes accounted for 10.8%. For children with PEP, we found no association between clinical characteristics and carrying either VT, NVT, or no pneumococcus.ConclusionCarriage of S. pneumoniae remains high among children hospitalized with ARI in Malawi, but children with VT carriage were no more likely to have PEP than children carrying no pneumococcus or those with NVT carriage. There were no differences in clinical characteristics between those carrying VT, NVT, or no pneumococcus.

Effect of pneumococcal conjugate vaccination on pneumococcal carriage in hospitalised children aged 2–59 months in Mongolia: an active pneumonia surveillance programme

Data on changes in pneumococcal serotypes in hospitalised children following the introduction of the pneumococcal conjugate vaccine (PCV) in low-income and middle-income countries are scarce. In 2016, Mongolia introduced the 13-valent PCV (PCV13) into the national immunisation programme. We aimed to describe the trend and impact of PCV13 introduction on pneumococcal carriage in hospitalised children aged 2-59months with pneumonia in Mongolia over a 6-year period. In this active surveillance programme, children aged 2-59months with pneumonia who met the study case definition (cough or difficulty breathing with either respiratory rate ≥50beats per min, oxygen saturation <90%, or clinical diagnosis of severe pneumonia) were enrolled between April 1, 2015, and June 30, 2021, from four districts in Ulaanbaatar. We tested nasopharyngeal samples collected at enrolment for pneumococci using lytA real-time quantitative PCR and conducted molecular serotyping and detection of antimicrobial resistance (AMR) genes with DNA microarray. We used log-binomial regression to estimate prevalence ratios (PRs) of pneumococcal carriage, comparing prevalence in the periods before and after the introduction of PCV13 and between vaccinated and unvaccinated children for three outcomes: overall, PCV13 vaccine-type, and non-PCV13 vaccine-type carriage. PRswere adjusted with covariates that were identified by use of a directed acyclic graph, informed by relevant literature. A total of 17 688 children were enrolled, of whom 17 607 (99·5%) met the study case criteria. 6545 (42·5%) of 15 411collected nasopharyngeal swabs were tested for pneumococci. In all age groups, a similar prevalence of pneumococcal carriage was shown between the pre-PCV13 period and post-PCV13 period (882 [48·0%] of 1837 vs 2174[46·2%] of 4708; adjusted PR 0·98 [95% CI 0·92-1·04]; p=0·60). Overall, vaccine-type carriage reduced by43·6% after the introduction of PCV13 (adjusted PR 0·56 [95% CI 0·51-0·62]; p<0·0001). Younger children (aged 2-23months) showed a 47·7% reduction in vaccine-type carriage (95% CI 41·2-53·5; adjusted PR 0·52 [95% CI 0·46-0·59]; p<0·0001), whereas children aged 24-59months had a 29·3% reduction (12·6-42·8; 0·71[0·57-0·87]; p=0·0014). Prevalence of 6A, 6B, 14, 19F, and 23F decreased following the introduction of PCV13; however, 19F and 6A remained common (5·8% and 2·9%). Non-vaccine-type carriage increased (adjusted PR 1·49[95% CI 1·32-1·67]), with 15A, NT2, and 15B/C being the most prevalent serotypes. Overall, 1761 (89·3%) of 1978analysed samples contained at least one AMR gene. The percentage of samples with any AMR gene decreased with vaccine introduction (92·3% in the pre-PCV13 period vs 85·3% in the post-PCV13 period; adjusted odds ratio 0·49 [95% CI 0·34-0·70]), with similar decreases for samples with at least three AMR genes (46·8% vs 27·6%; 0·44 [0·36-0·55]). 6 years after the introduction of PCV13 in Mongolia, the prevalence of vaccine-type carriage and AMR genes showed a reduction among young hospitalised children with pneumonia. Reductions in vaccine-type carriage are likely to result in reductions in pneumococcal pneumonia. GAVI, the Vaccine Alliance.

Impact of pneumococcal conjugate vaccines on invasive pneumococcal disease-causing lineages among South African children

Invasive pneumococcal disease (IPD) due to non-vaccine serotypes after the introduction of pneumococcal conjugate vaccines (PCV) remains a global concern. This study used pathogen genomics to evaluate changes in invasive pneumococcal lineages before, during and after vaccine introduction in South Africa. We included genomes (N = 3104) of IPD isolates from individuals aged <18 years (2005–20), spanning four periods: pre-PCV, PCV7, early-PCV13, and late-PCV13. Significant incidence reductions occurred among vaccine-type lineages in the late-PCV13 period compared to the pre-PCV period. However, some vaccine-type lineages continued to cause invasive disease and showed increasing effective population size trends in the post-PCV era. A significant increase in lineage diversity was observed from the PCV7 period to the early-PCV13 period (Simpson’s diversity index: 0.954, 95% confidence interval 0.948-0.961 vs 0.965, 0.962-0.969) supporting intervention-driven population structure perturbation. Increases in the prevalence of penicillin, erythromycin, and multidrug resistance were observed among non-vaccine serotypes in the late-PCV13 period compared to the pre-PCV period. In this work we highlight the importance of continued genomic surveillance to monitor disease-causing lineages post vaccination to support policy-making and future vaccine designs and considerations.

Reviewing the Pillars of Immunization: Essential Vaccines and Their Public Health Benefits.

Vaccination has lowered, across the globe, morbidity and mortality from infectious diseases. It is considered one of the basic principles of preventive health measures. The World Health Organization’s Expanded Programme on Immunization defined vaccinations that are required and their tremendous benefits to public health, which are discussed in this review article. These involve the vaccinations taken against most communicable diseases, such as COVID-19, polio, measles, rubella, pneumococcal diseases, rotavirus, human papillomavirus, tuberculosis, Haemophilus influenzae type B, diphtheria, pertussis, and tetanus. The article points out that quite a number of vaccinations have been proven effective and safe and if administered, could prevent serious disease, disability, and death. For example, vaccination against measles has been rated to be vital in the containment of outbreaks within nonimmune populations, while the DTP vaccine is paramount in decreasing the cases of pertussis, tetanus, and diphtheria. The effect of vaccination can be exemplified by the dramatic decrease in the occurrence of serious bacterial contagion in children since the introduction of conjugate vaccines against Hib and pneumococcus. Notwithstanding these successes, there are persistent obstacles, such as vaccine hesitancy, misinformation, and inequities in access to vaccines, all heightened by the COVID-19 pandemic. The article discusses the global impact of vaccination efforts under siege and appeals for further public health efforts toward the attainment of these goals.

Nasopharyngeal carriage of Streptococcus pneumoniae among children aged 30 days to &lt;60 months in Beijing and Shenzhen, China (2018–2021) during pneumococcal conjugate vaccine introduction and the coronavirus disease (COVID-19) pandemic

ObjectivesTo describe the carriage rate, serotype distribution, and antimicrobial susceptibility patterns of Streptococcus pneumoniae (S. pneumoniae) nasopharyngeal (NP) isolates among healthy children aged 30 days to &amp;lt;60 months in the cities of Beijing and Shenzhen during 2018–2021.MethodsA NP swab sample was collected among four annual cohorts of healthy children at routine well-child visits. S. pneumoniae was identified by culture, optochin sensitivity and bile solubility, serotypes determined by latex agglutination and Quellung, and antimicrobial susceptibility testing performed using E-test strips.ResultsS. pneumoniae NP carriage was 13.1% (645/4,911), with the highest S. pneumoniae carriage prevalence (15.3%) observed in 25 to &amp;lt;60 months. The carriage prevalence was 15.1% in children 13–24 months, 13.2% in children 7–12 months, and 8.2% in children 30 days to 6 months (P &amp;lt; 0.01). Living with siblings [20.0% vs. 9.4%: OR: 2.42 (95% CI: 2.05–2.87)] or attending day-care [31.8% vs. 11.3%: OR: 3.67 (95% CI: 2.94–4.57)] increased the risk (P &amp;lt; 0.01). During the period (January 2020–April 2021) of strict non-pharmaceutical interventions to prevent and control the COVID-19 pandemic, the proportion of children with S. pneumoniae colonization declined from 16.0% (94/587) to 5.8% (108/1,848) in Beijing while increasing from 14.5% (64/443) to 18.6% (379/2,033) in Shenzhen. Among S. pneumoniae isolates, 36.7% (237/645) belonged to 13-valent pneumococcal conjugate vaccine (PCV13) serotypes, 64.3% (408/645) were non-PCV13 serotypes, including 20.8% (134/645) non-serotypeable S. pneumoniae (NST). A total of 158/644 isolates (24.5%) were MDR. For the PCV13 isolates, MDR was detected in 36.3% (86/237) of isolates; in comparison, 17.6% (72/407) of non-PCV13 serotypes, including NST, were MDR (P &amp;lt; 0.01). S. pneumoniae NP carriage was detected in 10.7% of children with previous pneumococcal vaccination (PCV7 or PCV13 only) compared with 14.9% in children without previous pneumococcal vaccination.ConclusionsThe highest S. pneumoniae carriage prevalence were found in the oldest age group (25 to &amp;lt;60 months) and in children living with siblings or attending day-care. Vaccination with PCV7 or PCV13 was associated with lower PCV13-serotype colonization. In Beijing, S. pneumoniae carriage significantly declined during the COVID-19 pandemic.

Current and new vaccines against pneumococci

Pneumococcal vaccination plays acrucial role in the prevention of bacterial respiratory infections caused by Streptococcus pneumoniae. Pneumococci are responsible for diseases such as pneumonia, sinusitis and acute otitis media and can cause serious invasive infections such as meningitis and bacteraemia. Pneumococcal pneumonia leads to increased morbidity and mortality, particularly in patients with chronic lung diseases such as chronic obstructive pulmonary disease (COPD). The introduction of 13-valent conjugate vaccines (pneumococcal conjugate vaccine13 [PCV13]) has significantly reduced the burden of disease. However, infections caused by serotypes not covered by PCV13 continue to occur. Current vaccines such as the 20-valent conjugate vaccine (PCV20) provide extended serotype coverage and have shown arobust immune response in clinical trials. The recently updated recommendations of the German Standing Committee on Vaccination (Ständige Impfkommission, STIKO) include the use of PCV20 for all indication categories in adults, which represents asimplified and more effective vaccination strategy. Future developments include vaccines with even broader serotype coverage and improved immunological properties; these are expected to further reduce the burden of pneumococcal disease. Improving vaccination uptake and increasing vaccination rates, particularly among at-risk groups, remain key objectives to protect public health in the long term.

Re-evaluating the impact and cost-effectiveness of pneumococcal conjugate vaccine introduction in 112 low-income and middle-income countries in children younger than 5 years: a modelling study

Streptococcus pneumoniae has been estimated to cause 9·18 million cases of pneumococcal pneumonia, meningitis, and invasive non-pneumonia non-meningitis disease and 318 000 deaths among children younger than 5 years in 2015. We estimated the potential impact and cost-effectiveness of pneumococcal conjugate vaccine (PCV) introduction. We updated our existing pseudodynamic model to estimate the impact of 13-valent PCV (PCV13) in 112 low-income and middle-income countries by adapting our previously published pseudodynamic model with new country-specific evidence on vaccine coverage, burden, and post-introduction vaccine impact from WHO-UNICEF estimates of national immunisation coverage and a global burden study. Deaths, disability-adjusted life-years (DALYs), and cases averted were estimated for children younger than 5 years born between 2000 and 2030. We used specific PCV coverage in each country and a hypothetical scenario in which coverage increased to diphtheria-tetanus-pertussis (DTP) levels. We conducted probabilistic uncertainty analyses. Using specific vaccine coverage in countries, we estimated that PCV13 could prevent 697 000 (95% credibility interval 359 000-1 040 000) deaths, 46·0 (24·0-68·9) million DALYs, and 131 (89·0-172) million cases in 112 countries between 2000 and 2030. PCV was estimated to prevent 5·3% of pneumococcal deaths in children younger than 5 years during 2000-30. The incremental cost of vaccination would be I$851 (510-1530) per DALY averted. If PCV coverage were increased to DTP coverage in 2020, PCV13 could prevent an additional 146 000 (75 500-219 000) deaths. The inclusion of real-world evidence from lower-income settings revealed that delays in PCV roll-out globally and low PCV coverage have cost many lives. Countries with delays in vaccine introduction or low vaccine coverage have experienced many PCV-preventable deaths. These findings underscore the importance of rapidly scaling up PCV to achieve high coverage and maximise vaccine impact. Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance.

A perspective on the novel pentavalent Men5CV (NmCV-5) meningitis vaccine and Nigeria's pioneering rollout campaign.

The burden of meningitis poses great challenges for neurology and global health, manifesting with a range of symptoms from mild fever and headaches, to severe long term complications such as paralysis and cognitive impairment.. Unfortunately, those living in endemic regions, especially survivors, are often confronted with the harsh reality of reduced quality of life as measured by disability-adjusted life years. Meningitis is one of the leading causes of mortality and morbidity, especially in the meningitis belt of sub-Saharan Africa, with a recorded disease burden of over 2.5 million cases globally and children under five disproportionately impacted. This paper examines the global burden of meningitis, exploring its prevalence and impact across different regions. It further analyzes the evolution of vaccination strategies for meningitis prevention, emphasizing the recent development and introduction of the novel Men5CV meningococcal conjugate vaccine. Recurrent meningitis outbreaks across the meningitis belt have resulted in significant mortality over decades. A major turning point in the fight against the serogroup A epidemic was the development of the MenAfriVac vaccine, which resulted in declining cases. However, serogroups C, W, and X continue to pose problems. The novel pentavalent (Men5CV) vaccine has emerged as a remarkable advancement in the fight against meningitis, with its safety and effectiveness against a variety of serogroups, including the elusive serogroup X, demonstrated in clinical trials. Its pre-qualification by the World Health Organization (WHO), and subsequent recommendation for incorporation into routine immunization programs issued a new era with the potential for meningitis eradication. Nigeria now sets a benchmark for other nations in the meningitis zone, becoming the first country in the world to roll out the new Men5CV vaccines. Funding from organizations like Gavi, the Vaccine Alliance, highlights the importance of coordinated international efforts aligned with the WHO's roadmap for meningitis elimination by 2030. Stakeholder involvement, extensive immunization campaigns, and a strong healthcare infrastructure are all practical recommendations for public health integration.

Prevalence, serotype distribution, and antimicrobial susceptibility profile of Streptococcus pneumoniae in Sea Nomad children under 5 years of age in Wakatobi, Southeast Sulawesi, Indonesia: A cross-sectional study

ObjectiveIndonesia commenced the nationwide introduction of pneumococcal conjugate vaccine (PCV) in 2022. Pre-vaccine Streptococcus pneumoniae data from across the country could be critical to enable vaccine impact evaluation in the future. This study evaluates colonization prevalence, factors associated with colonization, serotype distribution, and the antimicrobial susceptibility profile of S. pneumoniae. MethodsChildren under 5 years of age were enrolled from Bajau tribe settlements in Wakatobi, southeast Sulawesi, Indonesia, from October 2018 to February 2019. Nasopharyngeal swab specimens were analysed by culture, and isolates were serotyped using sequential multiplex polymerase chain reaction. Antibiotic susceptibility was performed by the disk diffusion method. Multivariable logistic regression was performed for risk factor analysis. ResultsA total of 499 NP swab specimens were collected; 61.9% were colonized with S. pneumoniae and 48.9% of the isolates were of PCV13-vaccine type. The most common serotypes were 23F, 6B, 19F, and 6A at 13.2%, 9.8%, 8.9%, and 8.0%, respectively. Exposure to cigarette smoke in the household and runny nose were significant risk factors for colonization, with aORs of 1.6 (95% confidence interval: 1.1–2.3) and 2.1 (95% confidence interval: 1.4–3.3), respectively. ConclusionsThe findings of this study may contribute to baseline pre-vaccine data in Indonesia that would be critical for the impact evaluation of vaccines.

Sex-based difference in immune responses and efficacy of the pneumococcal conjugate vaccine.

Vaccine-mediated protection and susceptibility to Streptococcus pneumoniae (pneumococcus) infections are influenced by biological sex. The incidence of invasive pneumococcal disease remains higher in males compared to females even after the introduction of the pneumococcal conjugate vaccine (PCV). However, sex-based differences in the immune response to this conjugate vaccine remain unexplored. To investigate those differences, we vaccinated adult male and female mice with PCV and assessed cellular and humoral immune responses. Compared to females, male mice displayed lower levels of T follicular helper cells, germinal center B cells and plasmablasts, which are all required for antibody production following vaccination. This was linked to lower IgG and IgM levels against pneumococci and lower isotype switching to IgG3 in vaccinated males. Due to lower antibody levels, sera of vaccinated male mice had lower efficacy in several anti-pneumococcal functions including neutralization of bacterial binding to pulmonary epithelial cells as well as direct cytotoxicity against S. pneumoniae. Importantly, while the vaccine was highly protective in females, vaccinated males succumbed to infection more readily and were more susceptible to both lung-localized infection and systemic spread following S. pneumoniae challenge. These findings identify sex-based differences in immune responses to PCV that can inform future vaccine strategies.

Effect of pneumococcal conjugate vaccine six years post-introduction on pneumococcal carriage in Ulaanbaatar, Mongolia

Limited data from Asia are available on long-term effects of pneumococcal conjugate vaccine introduction on pneumococcal carriage. Here we assess the impact of 13-valent pneumococcal conjugate vaccine (PCV13) introduction on nasopharyngeal pneumococcal carriage prevalence, density and antimicrobial resistance. Cross-sectional carriage surveys were conducted pre-PCV13 (2015) and post-PCV13 introduction (2017 and 2022). Pneumococci were detected and quantified by real-time PCR from nasopharyngeal swabs. DNA microarray was used for molecular serotyping and to infer genetic lineage (Global Pneumococcal Sequence Cluster). The study included 1461 infants (5–8 weeks old) and 1489 toddlers (12–23 months old) enrolled from family health clinics. We show a reduction in PCV13 serotype carriage (with non-PCV13 serotype replacement) and a reduction in the proportion of samples containing resistance genes in toddlers six years post-PCV13 introduction. We observed an increase in pneumococcal nasopharyngeal density. Serotype 15 A, the most prevalent non-vaccine-serotype in 2022, was comprised predominantly of GPSC904;9. Reductions in PCV13 serotype carriage will likely result in pneumococcal disease reduction. It is important for ongoing surveillance to monitor serotype changes to potentially inform new vaccine development.

Epidemiological and bacterial profile ofchildhood meningitis in Tunisia.

The worldwide burden of disease of bacterial meningitis remains high, despite the decreasing incidence following introduction of routine vaccination campaigns.The aim of our study was to evaluate the epidemiological and bacteriological profile of paediatric bacterial meningitis (BM) in Tunisian children, during the period 2003-2019, following the implementation of Haemophilus influenzae type b (Hib) vaccine (April 2011) and before 10-valent pneumoccocal conjugate vaccine (PCV10) introduction to the childhood immunization program.All bacteriologically confirmed cases of BM admitted to children's hospital of Tunis were recorded (January 2003 to April 2019). Serogroups of Neisseria meningitidis (Nm) and serotypes of Streptococcus pneumoniae (Sp) and H. influenzae (Hi) and antibiotic resistance were determined using conventional and molecular methods.Among 388 cases, the most frequent species were Sp (51.3%), followed by Nm (27.5%) and Hi(16.8%). We observed a significant decrease in Hi BM rate during the conjugated Hib vaccine use period (P < 0.0001). The main pneumococcal serotypes were 14, 19F, 6B, 23F and 19A and the serotype coverage of PCV10, PCV13, PCV15 and PCV20 was 71.3 and 78.8%, 79.4 and 81.9% respectively. Themost frequent Nm serogroup was B (83.1%). Most Hi strains were of serotype b (86.9%). High levels of resistance were found: Sp and Nm to penicillin (respectively 60.1 and 80%) and Hi to ampicillin (42.6%). All meningococcal and Hi isolates were susceptible to third-generation cephalosporins and 7.2% of pneumococcal strains had decreased susceptibility to these antibiotics.The Hib conjugate vaccine decreased the rate of BM. Sp dominated the aetiology of BM in children in Tunisia. Conjugate vaccines introducing decreases not only BM cases but also antimicrobial resistance.

Economic Burden of Otitis Media Globally and an Overview of the Current Scenario to Alleviate the Disease Burden: A Systematic Review.

Introduction The prevalence of otitis media (OM) is substantial all over the world. Epidemiological data related to the economic burden of OM globally is minimal. The present systematic review was undertaken to estimate the economic burden of this disease in various parts of the world. Objectives An extensive literature search was done using PRISMA guidelines to identify relevant studies that estimated the economic burden of OM in monetary terms. The databases searched were PubMed Central, Ovid, and Embase. The cost estimation was done for one specific year and then compared considering the inflation rate. Data Synthesis The literature search led to the inclusion of 10 studies. The studies evaluated direct and indirect costs in monetary terms. Direct costs (health system and patient perspective) ranged from USD (United States Dollar) 122.64 (Netherlands) to USD 633.6 (USA) per episode of OM. Looking at only the patient perspective, the costs ranged from USD 19.32 (Oman) to USD 80.5 (Saudi Arabia). The total costs (direct and indirect) ranged from USD 232.7 to USD 977 (UK) per episode of OM. The economic burden per year was highest in the USA (USD 5 billion). The incidence of OM episodes was found more in children < 5 years old. Introduction of pneumococcal conjugate vaccines decreased the incidence in children and now the prevalence in adults is of concern. Conclusion The economic burden of OM is relatively high globally and addressing this public health burden is important. Approaches for the prevention, diagnosis, and treatment should be undertaken by the health system to alleviate this disease burden.

Expansion of pneumococcal serotype 23F and 14 lineages with genotypic changes in capsule polysaccharide locus and virulence gene profiles post introduction of pneumococcal conjugate vaccine in Blantyre, Malawi.

Since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Malawi in 2011, there has been persistent carriage of vaccine serotype (VT) Streptococcus pneumoniae, despite high vaccine coverage. To determine if there has been a genetic change within the VT capsule polysaccharide (cps) loci since the vaccine's introduction, we compared 1022 whole-genome-sequenced VT isolates from 1998 to 2019. We identified the clonal expansion of a multidrug-resistant, penicillin non-susceptible serotype 23F GPSC14-ST2059 lineage, a serotype 14 GPSC9-ST782 lineage and a novel serotype 14 sequence type GPSC9-ST18728 lineage. Serotype 23F GPSC14-ST2059 had an I253T mutation within the capsule oligosaccharide repeat unit polymerase Wzy protein, which is predicted in silico to alter the protein pocket cavity. Moreover, serotype 23F GPSC14-ST2059 had SNPs in the DNA binding sites for the cps transcriptional repressors CspR and SpxR. Serotype 14 GPSC9-ST782 harbours a non-truncated version of the large repetitive protein (Lrp), containing a Cna protein B-type domain which is also present in proteins associated with infection and colonisation. These emergent lineages also harboured genes associated with antibiotic resistance, and the promotion of colonisation and infection which were absent in other lineages of the same serotype. Together these data suggest that in addition to serotype replacement, modifications of the capsule locus associated with changes in virulence factor expression and antibiotic resistance may promote vaccine escape. In summary, the study highlights that the persistence of vaccine serotype carriage despite high vaccine coverage in Malawi may be partly caused by expansion of VT lineages post-PCV13 rollout.

Anticipated Effects of Higher-valency Pneumococcal Conjugate Vaccines on Colonization and Acute Otitis Media.

Bacterial etiologies of acute otitis media (AOM) have shifted from the introduction of pneumococcal conjugate vaccines (PCVs), antibiotic selection and competition among species. We characterized Streptococcus pneumoniae ( Spn ), Haemophilus influenzae ( Hflu ) and Moraxella catarrhalis ( Mcat ) in the nasopharynx during well-child healthy visits and at the onset of AOM, and in middle ear fluid (MEF) of children with AOM to assess anticipated effects of higher-valency PCVs (PCV15 and PCV20). From September 2021 to September 2023, we conducted a prospective longitudinal cohort study of PCV13 immunized children 6-36 months old. MEF was collected via tympanocentesis. Serotyping and antibiotic susceptibility testing were performed on Spn , Hflu and Mcat isolates. We obtained 825 nasopharyngeal and 216 MEF samples from 301 children. The order of frequency of nasopharyngeal colonization was Mcat , Spn and Hflu ; Hflu was the predominant otopathogen in MEF. Among Spn isolates, non-PCV15, non-PCV20 serotypes predominated in the nasopharynx and in MEF; the most frequent serotype was 35B. Among MEF samples, 30% of Spn isolates were amoxicillin nonsusceptible; 23% of Hflu isolates and 100% of Mcat isolates were β-lactamase-producing. The majority of Spn isolates among young children were non-PCV15, non-PCV20 serotypes, especially serotype 35B; therefore, the impact of higher-valency PCVs in reducing pneumococcal colonization or AOM is expected to be limited. Hflu continues to be the most frequent AOM pathogen. Antibiotic susceptibility data suggest a high dose of amoxicillin/clavulanate or alternative drugs that are effective against contemporary mix of otopathogens could be considered for optimal empiric selection to provide the best efficacy.

Evolution of invasive pneumococcal disease by serotype 3 in adults: a Spanish three-decade retrospective study

Invasive pneumococcal disease due to serotype 3 (S3-IPD) is associated with high mortality rates and long-term adverse effects. The introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the Spanish paediatric immunisation programme has not led to a decrease in the adult S3-IPD. We aimed to analyse the incidence, clinical characteristics and genomics of S3-IPD in adults in Spain. Adult IPD episodes hospitalized in a Southern Barcelona hospital were prospectively collected (1994-2020). For genomic comparison, S3-IPD isolates from six Spanish hospitals (2008-2020) and historical isolates (1989-1993) were analysed by WGS (Illumina and/or MinION). From 1994 to 2020, 270 S3-IPD episodes were detected. When comparing pre-PCV (1994-2001) and late-PCV13 (2016-2020) periods, only modest changes in S3-IPD were observed (from 1.58 to 1.28 episodes per 100,000 inhabitants year). In this period, the incidence of the two main lineages shifted from 0.38 to 0.67 (CC180-GPSC12) and from 1.18 to 0.55 (CC260-GPSC83). The overall 30-day mortality remained high (24.1%), though a decrease was observed between the pre-PCV (32.4%; 95.0% CI, 22.0-45.0) and the late-PCV13 period (16.7%; 95.0% CI, 7.5-32.0) (p=0.06). At the same time, comorbidities increased from 77.3% (95.0% CI, 65.0-86.0) to 85.7% (95.0% CI, 71.0-94.0) (p=0.69). There were no differences in clinical characteristics or 30-day mortality between the two S3 lineages. Although both lineages were genetically homogeneous, the CC180-GPSC12 lineage presented a higher SNP density, a more open pan-genome, and a major presence of prophages and mobile genetic elements carrying resistance genes. Adult S3-IPD remained stable in our area over the study period despite PCV13 introduction in children. However, a clonal shift was observed. The decrease in mortality rates and the increase in comorbidities suggest a change in clinical management and overall population characteristics. The low genetic variability and absence of clinical differences between lineages highlight the role of the S3 capsule in the disease severity. This study has been funded by Instituto de Salud Carlos III (ISCIII) "PI18/00339", "PI21/01000", "INT22/00096", "FI22/00279", CIBER "CIBERES-CB06/06/0037", "CIBERINFEC-CB21/13/00009" and MSD grant "IISP 60168".