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Background: 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 2-59 months with pneumonia in Mongolia over a 6-year period., Methods: In this active surveillance programme, children aged 2-59 months with pneumonia who met the study case definition (cough or difficulty breathing with either respiratory rate ≥50 beats 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. PRs were adjusted with covariates that were identified by use of a directed acyclic graph, informed by relevant literature., Findings: A total of 17 688 children were enrolled, of whom 17 607 (99·5%) met the study case criteria. 6545 (42·5%) of 15 411 collected 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 by 43·6% after the introduction of PCV13 (adjusted PR 0·56 [95% CI 0·51-0·62]; p<0·0001). Younger children (aged 2-23 months) 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 24-59 months 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 1978 analysed 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])., Interpretation: 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., Funding: GAVI, the Vaccine Alliance., Competing Interests: Declaration of interests CvM, MU, CDN, PB, BS, DL, CS, TM, and EKM are investigators on a Pfizer collaborative research project outside this work. EMD is currently employed by Pfizer. CS, EKM, and CDN are investigators on a Merck Investigator Studies Program grant funded by MSD outside this work. CS has participated in expert panels for MSD and Pfizer. CvM has participated in expert panels for Pfizer and Merck. JH is the co-founder and shareholder of BUGS Bioscience, a not-for-profit spinout company of St George's, University of London. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (© 2024. The Author(s).)

Background: Data available for RSV and influenza infections among children < 2 years in Mongolia are limited. We present data from four districts of Ulaanbaatar from April 2015 to June 2021., Methods: This study was nested in an enhanced surveillance project evaluating pneumococcal conjugate vaccine (PCV13) impact on the incidence of hospitalized lower respiratory tract infections (LRTIs). Our study was restricted to children aged < 2 years with arterial O 2 saturation < 93% and children with radiological pneumonia. Nasopharyngeal (NP) swabs collected at admission were tested for RSV and influenza using qRT-PCR. NP swabs of all patients with radiological pneumonia and of a subset of randomly selected NP swabs were tested for S. pneumoniae (S.p.) by qPCR and for serotypes by culture and DNA microarray., Results: Among 5705 patients, 2113 (37.0%) and 386 (6.8%) had RSV and influenza infections, respectively. Children aged 2-6 months had a higher percentage of very severe RSV infection compared to those older than 6 months (42.2% versus 31.4%, p-value Fisher's exact = 0.001). S.p. carriage was detected in 1073/2281 (47.0%) patients. Among S.p. carriage cases, 363/1073 (33.8%) had S.p. and RSV codetection, and 82/1073 (7.6%) had S.p. and influenza codetection. S.p. codetection with RSV/influenza was not associated with more severe LRTIs, compared to only RSV/influenza cases., Conclusion: In Mongolia, RSV is an important pathogen causing more severe LRTI in children under 6 months of age. Codetection of RSV or influenza virus and S.p. was not associated with increased severity., (© 2024 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Objectives: Limited 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., Methods: Our 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., Results: Among 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., Conclusions: No significant reductions were observed in any outcomes associated with RSV and influenza after PCV introduction., Competing Interests: The authors have no competing interests to declare., (© 2024 The Authors.)

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.

Importance: Streptococcus pneumoniae (the pneumococcus) is a bacterial pathogen with the greatest burden of disease in Asia and Africa. The pneumococcal capsular polysaccharide has biological relevance as a major virulence factor as well as public health importance as it is the target for currently licensed vaccines. These vaccines have limited valency, covering up to 23 of the >100 known capsular types (serotypes) with higher valency vaccines in development. Here, we have characterized a new pneumococcal serotype, which we have named 33G. We detected serotype 33G in nasopharyngeal swabs ( n = 20) from children and adults hospitalized with pneumonia, as well as healthy children in Mongolia. We show that the genetic, serological, and biochemical properties of 33G differ from existing serotypes, satisfying the criteria to be designated as a new serotype. Future studies should focus on the geographical distribution of 33G and any changes in prevalence following vaccine introduction., Competing Interests: C.V.M., E.K.M., T.M., B.D.G., and C.S. are investigators on a clinical research collaboration with Pfizer on PCV vaccination in Mongolia from which the isolates used in this study are derived. Salary support was received through the institutions. C.S. and E.K.M. are investigators on a Merck Investigator Studies Program grant funded by MSD for a study unrelated to this work. S.M., C.V.M., and C.S. have received honoraria [Pfizer (C.S., S.M., and C.V.M.) and MSD (C.S.)] for presentations at symposia or attendance at expert advisory meetings unrelated to this study. M.H. is an investigator on a research grant funded by Pfizer for a study unrelated to this work. E.M.D. and B.D.G. are employed by Pfizer and may hold Pfizer stock or stock options.

Background: Few studies have assessed the potential indirect effects of childhood pneumococcal conjugate vaccine (PCV) programs on the adult pneumonia burden in resource-limited settings. We evaluated the impact of childhood PCV13 immunisation on adult all-cause pneumonia following a phased program introduction from 2016., Methods: We conducted a time-series analysis to assess changes in pneumonia hospitalisation incidence at four district hospitals in Mongolia. Adults (≥18 years) that met the clinical case definition for all-cause pneumonia were enrolled. A negative binomial mixed-effects model was used to assess the impact of PCV13 introduction on monthly counts of pneumonia admissions from January 2015-February 2022. We also performed a restricted analysis excluding the COVID-19 pandemic period. All models were stratified by age and assessed separately. Additional analyses assessed the robustness of our findings., Findings: The average annual incidence of all-cause pneumonia hospitalisation was highest in adults 65+ years (62.81 per 10,000 population) and declined with decreasing age. After adjusting for the COVID-19 pandemic period, we found that rates of pneumonia hospitalisation remained largely unchanged over time. We did not observe a reduction in pneumonia hospitalisation in any age group. Results from restricted and sensitivity analyses were comparable to the primary results, finding limited evidence of a reduced pneumonia burden., Interpretation: We did not find evidence of indirect protection against all-cause pneumonia in adults following childhood PCV13 introduction. Direct pneumococcal vaccination and other interventions should be considered to reduce burden of pneumonia among older adults., Funding: Pfizer clinical research collaboration agreement (contract number: WI236621)., Competing Interests: EKM and CVM are lead investigators of this study through Murdoch Childrens Research Institute, which was funded by Pfizer. MU, BS, DL, PB, BT, DN, CDN, and TM are investigators on this collaborative research project funded by Pfizer. EMD, KEA, and BDG are employees of Pfizer and own Pfizer stock or stock options. The other authors have no relevant conflicts of interest to declare. This study is a Murdoch Childrens Research Institute-sponsored study which is investigator-led, and funded under a collaborative agreement by Pfizer Inc., (© 2023 The Authors.)

Background: Community-acquired pneumonia is a leading cause of morbidity and mortality among children and adults worldwide. Adult pneumonia surveillance remains limited in many low- and middle-income settings, resulting in the disease burden being largely unknown., Methods: A retrospective cohort study was conducted by reviewing medical charts for respiratory admissions at four district hospitals in Ulaanbaatar during January 2015-February 2019. Characteristics of community-acquired pneumonia cases were summarized by disease severity and age. To explore factors associated with severe pneumonia, we ran univariable and age-adjusted logistic regression models. Incidence rates were calculated using population denominators., Results: In total, 4290 respiratory admissions met the case definition for clinical pneumonia, including 430 admissions of severe pneumonia. The highest proportion of severe pneumonia admissions occurred in adults >65 years (37.4%). After adjusting for age, there were increased odds of severe pneumonia in males (adjusted odds ratio [aOR]: 1.63; 95% confidence interval [CI]: 1.33-2.00) and those with ≥1 underlying medical condition (aOR: 1.46; 95% CI: 1.14-1.87). The incidence of hospitalized pneumonia in adults ≥18 years increased from 13.49 (95% CI: 12.58-14.44) in 2015 to 17.65 (95% CI: 16.63-18.71) in 2018 per 10,000 population. The incidence of severe pneumonia was highest in adults >65 years, ranging from 9.29 (95% CI: 6.17-13.43) in 2015 to 12.69 (95% CI: 9.22-17.04) in 2018 per 10,000 population., Interpretations: Vaccination and other strategies to reduce the risk of pneumonia, particularly among older adults and those with underlying medical conditions, should be prioritized., Funding: Pfizer clinical research collaboration agreement (contract number: WI236621)., Competing Interests: EKM and CVM are lead investigators of this study through Murdoch Childrens Research Institute, which was funded by Pfizer. MU, CDN, BS, DL, BP and TM are investigators on this collaborative research project funded by Pfizer. BDG and EMD are employees of Pfizer and own Pfizer stock or stock options. The other authors have no relevant conflicts of interest to declare. This study is a Murdoch Childrens Research Institute-sponsored study which is investigator-led, and funded under a collaborative agreement by Pfizer Inc., (© 2022 The Author(s).)