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Maeda H, Morimoto K. Global distribution and characteristics of pneumococcal serotypes in adults. Hum Vaccin Immunother 2025; 21:2469424. [PMID: 40015240 PMCID: PMC11869777 DOI: 10.1080/21645515.2025.2469424] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 02/11/2025] [Accepted: 02/17/2025] [Indexed: 03/01/2025] Open
Abstract
The introduction of pneumococcal conjugate vaccines (PCVs) into pediatric national immunization programs (NIP) has significantly reduced invasive pneumococcal diseases and pneumococcal pneumonia caused by PCV serotypes in adults due to herd immunity. However, diseases caused by PCV13 serotypes persist, mainly serotype 3, known for its severity. With the reduction in PCV13 serotypes, diseases caused by non-PCV13 serotypes increased. Residual and emerging serotypes vary regionally; serotype 8 in Europe and South Africa, and serotype 4 in the US and Canada. PCV20 and PCV21 were recently developed, which can prevent residual and emerging pneumococcal diseases where herd immunity is well-established. In countries that have not introduced PCV into pediatric NIP, the pneumococcal disease burden due to PCV serotypes is still marked. Given that serotype distribution varies by region and evolves over time, this review aimed to discuss serotype distribution and disease severity in adults across countries to support future pneumococcal vaccine strategies.
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Affiliation(s)
- Haruka Maeda
- Department of Respiratory Infections, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
| | - Konosuke Morimoto
- Department of Respiratory Infections, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
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2
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Sidorenko SV, Rennert W, Zhdanov KV, Lobzin YV, Nikitina EV, Ageevets VA, Martens EA, Rybalko DS, Kalinogorskaya OS, Goncharova AR, Goncharov NE, Tsvetkova IA, Kraeva LA, Zhimbayeva OB, Andreeva AN, Ardysheva AT, Bayazitova LT, Beissegulova GN, Bikmieva AV, Bolgarova EV, Brzhozovskaya EA, Burkutbayeva TN, Feldblum IV, Girina AA, Gordeeva SA, Hanenko ON, Illarionova TV, Sh Isaeva G, Klimashina AV, Kolomiets ND, Koloskova YA, Kovalishena OV, Kozeeva TG, Mayanskiy NA, Mustafina KK, Nemirovchenko IA, Petrova LY, Pozdeeva IV, Ramazanova BA, Romanova ON, Salina VA, Seitkhanova BT, Shirokova IY, Sokolova NV, Tomracheva LV, Tonko OV, Tyurin YA, Venchakova VV, Verentsova IV, Yeraliyeva LT, Zakharova YA. Serotype dynamics of Streptococcus pneumoniae in some countries in Eastern Europe and Central Asia. Vaccine 2025; 57:127213. [PMID: 40347708 DOI: 10.1016/j.vaccine.2025.127213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 04/10/2025] [Accepted: 05/01/2025] [Indexed: 05/14/2025]
Abstract
The burden of pneumococcal disease remains a global challenge. The purpose of this work was to assess the serotype composition of S. pneumoniae circulating among children under 5 years of age in Eastern European (the Russian Federation and the Republic of Belarus) and Central Asian (the Republic of Kazakhstan) countries which are characterized by close cultural and economic ties. The most pronounced changes were noted in the Russian Federation. In the pre-vaccination period (before 2015) PCV13 covered 66 % - 90 % of prevalent serotypes. In 2016-2018 coverage decreased to 59.2 %. During this study period (2020-2023) PCV 13 related serotypes in healthy children and those with respiratory infections dropped further to 23.2 % and 35.7 %, respectively. In Kazakhstan, vaccine-related serotypes among healthy children and children with RTI were more prevalent than in Russia (51.5-58.6 % vs 23.2-35.7 %) despite both countries having introduced pneumococcal vaccination at the same time, and both countries reporting vaccination rates above 90 % in children under 5 years of age. In the Republic of Belarus, in the absence of a universal vaccination program, PCV13 covers 86.4 % of serotypes. Serotypes 19F (31 %), 3 (16.2 %), 19 A (10.3 %), and 14 (10 %) predominate among S. pneumoniae causing acute otitis media in children. Expanding the serotype/serogroup composition of new vaccines may provide protection against potentially invasive non-vaccine strains in the future.
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Affiliation(s)
- Sergey V Sidorenko
- Pediatric Research and Clinical Center for Infectious Diseases, North-Western State Medical University named after I. I. Mechnikov, Kirochnaya Ulitsa, 41, St Petersburg 191015, Russia
| | - Wolfgang Rennert
- Rostropovich Vishnevskaya Foundation, 1717 K Street, N.W., Suite 900, Washington, DC 20006, USA; Georgetown University Hospital Department of Pediatrics, 4200 Wisconsin Ave, NW, Suite 200, Washington, DC 20016, USA.
| | - Konstantin V Zhdanov
- Pediatric Research and Clinical Center for Infectious Diseases, North-Western State Medical University named after I. I. Mechnikov, Kirochnaya Ulitsa, 41, St Petersburg 191015, Russia
| | - Yuri V Lobzin
- Pediatric Research and Clinical Center for Infectious Diseases, North-Western State Medical University named after I. I. Mechnikov, Kirochnaya Ulitsa, 41, St Petersburg 191015, Russia
| | - Ekaterina V Nikitina
- Pediatric Research and Clinical Center for Infectious Diseases, North-Western State Medical University named after I. I. Mechnikov, Kirochnaya Ulitsa, 41, St Petersburg 191015, Russia
| | - Vladimir A Ageevets
- Pediatric Research and Clinical Center for Infectious Diseases, North-Western State Medical University named after I. I. Mechnikov, Kirochnaya Ulitsa, 41, St Petersburg 191015, Russia
| | - Elvira A Martens
- Pediatric Research and Clinical Center for Infectious Diseases, North-Western State Medical University named after I. I. Mechnikov, Kirochnaya Ulitsa, 41, St Petersburg 191015, Russia
| | - Daria S Rybalko
- Pediatric Research and Clinical Center for Infectious Diseases, North-Western State Medical University named after I. I. Mechnikov, Kirochnaya Ulitsa, 41, St Petersburg 191015, Russia
| | - Olga S Kalinogorskaya
- Pediatric Research and Clinical Center for Infectious Diseases, North-Western State Medical University named after I. I. Mechnikov, Kirochnaya Ulitsa, 41, St Petersburg 191015, Russia
| | - Alina R Goncharova
- Pediatric Research and Clinical Center for Infectious Diseases, North-Western State Medical University named after I. I. Mechnikov, Kirochnaya Ulitsa, 41, St Petersburg 191015, Russia; Saint-Petersburg Pasteur Institute, Ulitsa Mira, 14, St Petersburg 197101, Russia
| | - Nikita E Goncharov
- Saint-Petersburg Pasteur Institute, Ulitsa Mira, 14, St Petersburg 197101, Russia
| | - Irina A Tsvetkova
- Pediatric Research and Clinical Center for Infectious Diseases, North-Western State Medical University named after I. I. Mechnikov, Kirochnaya Ulitsa, 41, St Petersburg 191015, Russia; St. Petersburg State Pediatric Medical University, Litovskaya Ulitsa, 2, St Petersburg 194100, Russia
| | - Lyudmila A Kraeva
- Saint-Petersburg Pasteur Institute, Ulitsa Mira, 14, St Petersburg 197101, Russia; Military Medical Academy named after S.M. Kirov, 6, Academika Lebedeva Street, St Petersburg 194044, Russia
| | - Oyuna B Zhimbayeva
- Saint-Petersburg Pasteur Institute, Ulitsa Mira, 14, St Petersburg 197101, Russia.
| | - Anna N Andreeva
- Pediatric Research and Clinical Center for Infectious Diseases, North-Western State Medical University named after I. I. Mechnikov, Kirochnaya Ulitsa, 41, St Petersburg 191015, Russia
| | - Anastasia T Ardysheva
- Perm Clinical Center of the Federal Medical and Biological Agency, Tselinnaya Str, 27, Perm 614056, Russia
| | - Lira T Bayazitova
- Kazan Scientific Research Institute of Epidemiology and Microbiology, Kazan State Medical University named after Academician V.M. Aristovsky, Butlerova Str, 49, Kazan 420012, Russia
| | - Gulzhan N Beissegulova
- Asfendiyarov Kazakh National Medical University, Tole Bi Str, 94, Almaty 050000, Kazakhstan.
| | - Alina V Bikmieva
- E.A.Vagner Perm State Medical University, Ulitsa Kuybysheva, 39, Perm 614000, Russia
| | - Ekaterina V Bolgarova
- Federal Scientific Research Institute of Viral Infections "Virome", Letnaya Str, Ekatarinburg 620030, Russia
| | - Ekaterina A Brzhozovskaya
- Russian Children's Clinical Hospital of Pirogov Russian National Research Medical University, Ulitsa Taldomskaya, 2, Moscow 125412, Russia
| | - Tatyana N Burkutbayeva
- Asfendiyarov Kazakh National Medical University, Tole Bi Str, 94, Almaty 050000, Kazakhstan
| | - Irina V Feldblum
- E.A.Vagner Perm State Medical University, Ulitsa Kuybysheva, 39, Perm 614000, Russia
| | - Asiya A Girina
- Khanty-Mansiysk State Medical Academy, Ulitsa Mira, 40, Khanty-Mansiysk, Khanty-Mansiyskiy Avtonomnyy Okrug, 628011, Russia
| | - Svetlana A Gordeeva
- Clinical Infectious Diseases Hospital named after S.P. Botkin, Piskaryovskiy Avenue, 49, St Petersburg 195067, Russia
| | - Oksana N Hanenko
- Belarusian State Medical University, Prospekt Dzerzhinskogo 83, Minsk, Minskaja Voblasc 220116, Belarus
| | - Tatyana V Illarionova
- Privolzhsky Research Medical University, Minin and Pozharsky Sq, 10/1, Nizhny Novgorod, Nizhny Novgorod Oblast, 603005, Russia
| | - Guzel Sh Isaeva
- Kazan Scientific Research Institute of Epidemiology and Microbiology, Kazan State Medical University named after Academician V.M. Aristovsky, Butlerova Str, 49, Kazan 420012, Russia
| | - Alla V Klimashina
- Perm Clinical Center of the Federal Medical and Biological Agency, Tselinnaya Str, 27, Perm 614056, Russia
| | - Natalia D Kolomiets
- Belarusian State Medical University, Prospekt Dzerzhinskogo 83, Minsk, Minskaja Voblasc 220116, Belarus
| | - Yekaterina A Koloskova
- Asfendiyarov Kazakh National Medical University, Tole Bi Str, 94, Almaty 050000, Kazakhstan.
| | - Olga V Kovalishena
- Privolzhsky Research Medical University, Minin and Pozharsky Sq, 10/1, Nizhny Novgorod, Nizhny Novgorod Oblast, 603005, Russia
| | - Tatyana G Kozeeva
- Perm Clinical Center of the Federal Medical and Biological Agency, Tselinnaya Str, 27, Perm 614056, Russia
| | - Nikolay A Mayanskiy
- Russian Children's Clinical Hospital of Pirogov Russian National Research Medical University, Ulitsa Taldomskaya, 2, Moscow 125412, Russia
| | - Kamilya K Mustafina
- Asfendiyarov Kazakh National Medical University, Tole Bi Str, 94, Almaty 050000, Kazakhstan.
| | - Ilya A Nemirovchenko
- Privolzhsky Research Medical University, Minin and Pozharsky Sq, 10/1, Nizhny Novgorod, Nizhny Novgorod Oblast, 603005, Russia
| | - Lyudmila Y Petrova
- Clinical Infectious Diseases Hospital named after S.P. Botkin, Piskaryovskiy Avenue, 49, St Petersburg 195067, Russia
| | - Irina V Pozdeeva
- District Clinical Hospital of the Khanty-Mansiysk Autonomous Okrug - Ugra, Barabinskaya Ulitsa, 12, Khanty-Mansiysk, Khanty-Mansiyskiy avtonomnyy okrug, 628001, Russia
| | - Bakhyt A Ramazanova
- Asfendiyarov Kazakh National Medical University, Tole Bi Str, 94, Almaty 050000, Kazakhstan.
| | - Oksana N Romanova
- Belarusian State Medical University, Prospekt Dzerzhinskogo 83, Minsk, Minskaja Voblasc 220116, Belarus.
| | - Valentina A Salina
- Privolzhsky Research Medical University, Minin and Pozharsky Sq, 10/1, Nizhny Novgorod, Nizhny Novgorod Oblast, 603005, Russia
| | | | - Irina Y Shirokova
- Privolzhsky Research Medical University, Minin and Pozharsky Sq, 10/1, Nizhny Novgorod, Nizhny Novgorod Oblast, 603005, Russia
| | - Natalia V Sokolova
- Perm Clinical Center of the Federal Medical and Biological Agency, Tselinnaya Str, 27, Perm 614056, Russia
| | - Lyudmila V Tomracheva
- Khanty-Mansiysk State Medical Academy, Ulitsa Mira, 40, Khanty-Mansiysk, Khanty-Mansiyskiy Avtonomnyy Okrug, 628011, Russia
| | - Oksana V Tonko
- Belarusian State Medical University, Prospekt Dzerzhinskogo 83, Minsk, Minskaja Voblasc 220116, Belarus
| | - Yuri A Tyurin
- Kazan Scientific Research Institute of Epidemiology and Microbiology, Kazan State Medical University named after Academician V.M. Aristovsky, Butlerova Str, 49, Kazan 420012, Russia
| | - Valentina V Venchakova
- Pediatric Research and Clinical Center for Infectious Diseases, North-Western State Medical University named after I. I. Mechnikov, Kirochnaya Ulitsa, 41, St Petersburg 191015, Russia
| | - Irina V Verentsova
- District Clinical Hospital of the Khanty-Mansiysk Autonomous Okrug - Ugra, Barabinskaya Ulitsa, 12, Khanty-Mansiysk, Khanty-Mansiyskiy avtonomnyy okrug, 628001, Russia
| | - Lyazzat T Yeraliyeva
- National Academy of Sciences under the President of the Republic of Kazakhstan, 28 Shevchenko Str, Almaty 050010, Kazakhstan
| | - Yuliya A Zakharova
- F.F. Erisman Federal Scientific Centre of Hygiene Rospotrebnadzor, Semashko Str, 2, Moscow 141000, Russia.
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Ntim OK, Donkor ES. Molecular Epidemiology of Streptococcus pneumoniae Serotype 1: A Systematic Review of Circulating Clones and Clonal Clusters. Int J Mol Sci 2025; 26:2266. [PMID: 40076900 PMCID: PMC11900055 DOI: 10.3390/ijms26052266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/23/2025] [Accepted: 01/29/2025] [Indexed: 03/14/2025] Open
Abstract
Streptococcus pneumoniae serotype 1 is one of the most prevalent serotypes commonly associated with invasive pneumococcal disease cases and outbreaks worldwide. Several sequence types of this serotype have been identified globally, including those exhibiting both high virulence potential and antimicrobial resistance profiles. This systematic review presents the global distribution of clones of pneumococcal serotype 1, describing their circulating patterns in various regions in the world. A database search was conducted in Google Scholar, PubMed, Scopus, ScienceDirect, and Web of Science using keywords related to Streptococcus pneumoniae serotype 1. The inclusion criteria entailed peer-reviewed studies published in English describing the utilization of at least one molecular genotyping tool to identify S. pneumoniae serotype 1 clones based on their sequence types. Data extracted were managed and analyzed using Microsoft Excel 365 (Version 2108). Forty-three studies were finally included in the systematic review. A total of 103 MLST serotype 1 sequence types were identified in 48 countries. These clones were widely reported to be associated with invasive pneumococcal diseases. Globally, ST217 and ST306 clonal complexes (CC217 and CC306) were the predominant lineages of serotype 1 sequence types, exhibiting distinct continental distribution patterns. CC217, characterized by ST217, ST303, ST612, ST618, and ST3081, was predominant in Africa and Asia. ST306 clonal complex, which is grouped into ST306, ST304, and ST227 were mostly found in Europe, Oceania, North America, and some countries in South America. ST615 was predominant in Chile, Peru, and Argentina. The hypervirulence nature of serotype 1, coupled with its complex genetic diversity, poses a significant public health threat. Our findings emphasize the need for enhanced surveillance and targeted interventions to mitigate the spread of these hypervirulent clones, ultimately informing evidence-based strategies for disease prevention and control.
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Affiliation(s)
| | - Eric S. Donkor
- Department of Medical Microbiology, University of Ghana Medical School, Korle Bu, Accra P.O. Box KB 4236, Ghana
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Ridelfi M, Pierleoni G, Zucconi Galli Fonseca V, Batani G, Rappuoli R, Sala C. State of the Art and Emerging Technologies in Vaccine Design for Respiratory Pathogens. Semin Respir Crit Care Med 2025. [PMID: 39870103 DOI: 10.1055/a-2500-1878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2025]
Abstract
In this review, we present the efforts made so far in developing effective solutions to prevent infections caused by seven major respiratory pathogens: influenza virus, respiratory syncytial virus (RSV), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Bordetella pertussis, Streptococcus pneumoniae (pneumococcus), Mycobacterium tuberculosis, and Pseudomonas aeruginosa. Advancements driven by the recent coronavirus disease 2019 (COVID-19) crisis have largely focused on viruses, but effective prophylactic solutions for bacterial pathogens are also needed, especially in light of the antimicrobial resistance (AMR) phenomenon. Here, we discuss various innovative key technologies that can help address this critical need, such as (a) the development of Lung-on-Chip ex vivo models to gain a better understanding of the pathogenesis process and the host-microbe interactions; (b) a more thorough investigation of the mechanisms behind mucosal immunity as the first line of defense against pathogens; (c) the identification of correlates of protection (CoPs) which, in conjunction with the Reverse Vaccinology 2.0 approach, can push a more rational and targeted design of vaccines. By focusing on these critical areas, we expect substantial progress in the development of new vaccines against respiratory bacterial pathogens, thereby enhancing global health protection in the framework of the increasingly concerning AMR emergence.
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Affiliation(s)
- Matteo Ridelfi
- Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
| | - Giulio Pierleoni
- Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
| | | | - Giampiero Batani
- Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
| | | | - Claudia Sala
- Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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Ning X, Li L, Liu J, Wang F, Tan K, Li W, Zhou K, Jing S, Lin A, Bi J, Zhao S, Deng H, Zhu C, Lv S, Li J, Liang J, Zhao Q, Wang Y, Chen B, Zhu L, Shen G, Liu J, Li Z, Deng J, Zhao X, Shan M, Wang Y, Liu S, Jiang T, Chen X, Zhang Y, Cai S, Wang L, Lu X, Jiang J, Dong F, Ye L, Sun J, Yao K, Yang Y, Liu G. Invasive pneumococcal diseases in Chinese children: a multicentre hospital-based active surveillance from 2019 to 2021. Emerg Microbes Infect 2024; 13:2332670. [PMID: 38646911 PMCID: PMC11047219 DOI: 10.1080/22221751.2024.2332670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Accepted: 03/15/2024] [Indexed: 04/23/2024]
Abstract
This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12-46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.
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Affiliation(s)
- Xue Ning
- Key Laboratory of Major Diseases in Children, Ministry of Education, Department of Infectious Diseases, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Lianmei Li
- Department of Infectious and Digestive Diseases, Qinghai Province Women and Children's Hospital, Xining, People’s Republic of China
| | - Jing Liu
- Department of Infectious Diseases, Hunan Children’s Hospital, Changsha, People’s Republic of China
| | - Fang Wang
- Department of Infectious Diseases, Henan Children’s Hospital, (Children's Hospital Affiliated of Zhengzhou University, Zhengzhou Children's Hospital), Zhengzhou, People’s Republic of China
| | - Kun Tan
- Department of Infectious Diseases, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China
| | - Wenhui Li
- Department of Infectious and Digestive Diseases, Children’s Hospital of Hebei Province, Shijiazhuang, People’s Republic of China
| | - Kai Zhou
- Department of Infectious Diseases, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Shujun Jing
- Department of Infectious Diseases, Dalian Children’s Hospital, Dalian, People’s Republic of China
| | - Aiwei Lin
- Department of Infectious Diseases, Children’s Hospital Affiliated to Shandong University, Jinan, People’s Republic of China
- Jinan Children’s Hospital, Shandong University, Jinan, People’s Republic of China
| | - Jing Bi
- Department of Infectious Diseases, Baoding Children’s Hospital, Baoding, People’s Republic of China
| | - Shiyong Zhao
- Department of Infectious Diseases, Hangzhou Children’s Hospital, Hangzhou, People’s Republic of China
| | - Huiling Deng
- Department of Infectious Diseases, Xian Children’s Hospital, Xian, People’s Republic of China
| | - Chunhui Zhu
- Department of Infectious Diseases, Children’s Hospital of Jiangxi Province, Nanchang, People’s Republic of China
| | - Shanshan Lv
- Department of Infectious Diseases, Changchun Children’s Hospital, Changchun, People’s Republic of China
| | - Juan Li
- Department of Infectious Diseases, Urumqi Children’s Hospital, Urumqi, People’s Republic of China
| | - Jun Liang
- Department of Pediatric Intensive Care Unit, People’s Hospital of Liaocheng, Liaocheng, People’s Republic of China
| | - Qing Zhao
- Department of Infectious Diseases, Children’s Hospital of Shanxi Province, Taiyuan, People’s Republic of China
| | - Yumin Wang
- Department of Infectious Diseases, Maternal and Child Health Care Hospital of the Inner Mongolia autonomous region, Huhehaote, People’s Republic of China
| | - Biquan Chen
- Department of Infectious Diseases, Anhui Provincial Children’s Hospital, Hefei, People’s Republic of China
| | - Liang Zhu
- Key Laboratory of Major Diseases in Children, Ministry of Education, Department of Infectious Diseases, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Guowu Shen
- Department of clinical laboratory, Qinghai Province Women and Children's Hospital, Xining, People’s Republic of China
| | - Jianlong Liu
- Department of clinic laboratory, Hunan Children’s Hospital, Changsha, People’s Republic of China
| | - Zhi Li
- Department of Infectious Diseases, Henan Children’s Hospital, (Children's Hospital Affiliated of Zhengzhou University, Zhengzhou Children's Hospital), Zhengzhou, People’s Republic of China
| | - Jikui Deng
- Department of Infectious Diseases, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China
| | - Xin Zhao
- Department of Infectious and Digestive Diseases, Children’s Hospital of Hebei Province, Shijiazhuang, People’s Republic of China
| | - Mingfeng Shan
- Department of Infectious Diseases, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Yi Wang
- Department of Infectious Diseases, Dalian Children’s Hospital, Dalian, People’s Republic of China
| | - Shihua Liu
- Department of Infectious Diseases, Children’s Hospital Affiliated to Shandong University, Jinan, People’s Republic of China
- Jinan Children’s Hospital, Shandong University, Jinan, People’s Republic of China
| | - Tingting Jiang
- Department of Infectious Diseases, Baoding Children’s Hospital, Baoding, People’s Republic of China
| | - Xuexia Chen
- Department of Infectious Diseases, Hangzhou Children’s Hospital, Hangzhou, People’s Republic of China
| | - Yufeng Zhang
- Department of Infectious Diseases, Xian Children’s Hospital, Xian, People’s Republic of China
| | - Sha Cai
- Department of Infectious Diseases, Children’s Hospital of Jiangxi Province, Nanchang, People’s Republic of China
| | - Lixue Wang
- Department of Infectious Diseases, Changchun Children’s Hospital, Changchun, People’s Republic of China
| | - Xudong Lu
- Department of Infectious Diseases, Urumqi Children’s Hospital, Urumqi, People’s Republic of China
| | - Jinghui Jiang
- Department of Pediatric Intensive Care Unit, People’s Hospital of Liaocheng, Liaocheng, People’s Republic of China
| | - Fang Dong
- Department of Infectious Diseases, Children’s Hospital of Shanxi Province, Taiyuan, People’s Republic of China
| | - Lan Ye
- Department of Infectious Diseases, Maternal and Child Health Care Hospital of the Inner Mongolia autonomous region, Huhehaote, People’s Republic of China
| | - Jing Sun
- Department of Infectious Diseases, Anhui Provincial Children’s Hospital, Hefei, People’s Republic of China
| | - Kaihu Yao
- Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children’s Hospital, National Center for Children’s Health, Capital Medical University, Beijing, People’s Republic of China
| | - Yonghong Yang
- Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children’s Hospital, National Center for Children’s Health, Capital Medical University, Beijing, People’s Republic of China
| | - Gang Liu
- Key Laboratory of Major Diseases in Children, Ministry of Education, Department of Infectious Diseases, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, People’s Republic of China
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Vestjens SMT, van Mens SP, Meek B, Lalmahomed TA, de Jong B, Goswami D, Vlaminckx BJM, Ahmed D, de Jongh BM, Endtz HP, Brooks WA, Rijkers GT. Streptococcus pneumoniae serotype distribution in Bangladeshi under-fives with community-acquired pneumonia pre-10-valent pneumococcal conjugate vaccination. Pneumonia (Nathan) 2024; 16:29. [PMID: 39497193 PMCID: PMC11536696 DOI: 10.1186/s41479-024-00152-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Accepted: 07/31/2024] [Indexed: 11/07/2024] Open
Abstract
BACKGROUND Streptococcus pneumoniae is the most frequent causative pathogen of bacterial pneumonia in children worldwide. Bangladesh introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in their national immunization program for infants in 2015. We assessed its potential coverage in under-fives with community-acquired pneumonia (CAP) in the years before PCV10 was introduced. METHODS A total of 1502 childhood pneumonia cases (< 5 year olds living in the urban section Kamalapur, Dhaka) were enrolled between 2011 and 2013. Acute phase and late (convalescent) serum samples were collected from 1380 cases. Serotype-specific pneumococcal antibody concentrations were measured using a 25-plex immunoassay panel. Pneumococcal CAP was diagnosed based on a serotype-specific pneumococcal antibody response. RESULTS S. pneumoniae was serologically identified as causative pathogen in 406/1380 (29%) cases. The five most prevalent serotypes were (in descending order) 11A, 22F, 3, 2 and 19F. Based on the percentage of pneumonia cases associated with PCV10 vaccine types, the potential PCV10 coverage was 29% (116/406). CONCLUSIONS In almost a third of the studied cases S. pneumoniae was identified as a causative pathogen. Because of the characteristics of the immunoassay, this might well be a gross underestimation. Nevertheless, the potential PCV10-coverage was low. Given the high serotype diversity, the region might benefit greatly from a higher-coverage PCV or recombinant protein vaccine.
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Affiliation(s)
- Stefan M T Vestjens
- Department of Medical Microbiology & Immunology, St. Antonius Hospital, Nieuwegein, The Netherlands.
- Department of Medical Microbiology & Immunology, Diakonessenhuis, Utrecht, The Netherlands.
| | - Suzan P van Mens
- Department of Medical Microbiology & Immunology, St. Antonius Hospital, Nieuwegein, The Netherlands
- Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht University Medical Center, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands
| | - Bob Meek
- Department of Medical Microbiology & Immunology, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - Tariq A Lalmahomed
- Science Department, University College Roosevelt, Middelburg, Nieuwegein, The Netherlands
| | - Ben de Jong
- Department of Medical Microbiology & Immunology, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - Doli Goswami
- International Center for Diarrhoeal Disease Research (icddr,b), Dhaka and Matlab, Bangladesh
| | - Bart J M Vlaminckx
- Department of Medical Microbiology & Immunology, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - Dilruba Ahmed
- International Center for Diarrhoeal Disease Research (icddr,b), Dhaka and Matlab, Bangladesh
| | - Bartelt M de Jongh
- Department of Medical Microbiology & Immunology, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - Hubert P Endtz
- International Center for Diarrhoeal Disease Research (icddr,b), Dhaka and Matlab, Bangladesh
- Department of Medical Microbiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - W Abdullah Brooks
- International Center for Diarrhoeal Disease Research (icddr,b), Dhaka and Matlab, Bangladesh
- Department of International Health, Johns Hopkins University, Baltimore, MD, USA
| | - Ger T Rijkers
- Department of Medical Microbiology & Immunology, St. Antonius Hospital, Nieuwegein, The Netherlands
- Science Department, University College Roosevelt, Middelburg, Nieuwegein, The Netherlands
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Passaris I, Depickère S, Braeye T, Mukovnikova M, Vodolazkaia A, Abels C, Cuypers L, Desmet S, Ceyssens PJ. Non-invasive Streptococcus pneumoniae infections are associated with different serotypes than invasive infections, Belgium, 2020 to 2023. Euro Surveill 2024; 29:2400108. [PMID: 39512163 PMCID: PMC11544722 DOI: 10.2807/1560-7917.es.2024.29.45.2400108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 05/02/2024] [Indexed: 11/15/2024] Open
Abstract
BackgroundDespite widely implemented pneumococcal vaccination programmes, Streptococcus pneumoniae remains a global risk for human health. Streptococcus pneumoniae can cause invasive (IPD) or non-invasive pneumococcal disease (NIPD). Surveillance is mainly focusing on IPD, assessing the full impact of pneumococcal vaccination programmes on pneumococcal disease is challenging.AimWe aimed to prospectively investigate serotype distribution and antimicrobial resistance (AMR) of S. pneumoniae isolates from patients with NIPD and compare with data on IPD isolates and with a 2007-2008 dataset on NIPD.MethodsBetween September 2020 and April 2023, we collected isolates and patient data from patients with NIPD from 23 clinical laboratories in Belgium. Capsular typing was performed by a validated Fourier-Transform Infrared spectroscopic method, and AMR was assessed with broth microdilution, using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints.ResultsWe received S. pneumoniae isolates from 1,008 patients with lower respiratory tract infections (n = 760), otitis media (n = 190) and sinusitis (n = 58). Serotype 3 was the most prevalent serotype among the NIPD isolates. Serotypes not included in the 20-valent pneumococcal conjugate vaccine (PCV20) were significantly more common among the NIPD than among the IPD isolates. Antimicrobial resistance levels were significantly higher among the NIPD isolates (n = 539; 2020-2022) compared with the IPD isolates (n = 2,344; 2021-2022). Resistance to several β-lactam antimicrobials had increased significantly compared with 15 years before.ConclusionsThe NIPD isolates were strongly associated with non-vaccine serotypes and with increased AMR levels. This underlines the importance of continued NIPD surveillance for informed policy making on vaccination programmes.
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Affiliation(s)
| | | | - Toon Braeye
- Epidemiology of Infectious Diseases, Sciensano, Brussels, Belgium
| | | | | | | | - Lize Cuypers
- Laboratory of Clinical Microbiology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- National Reference Centre for invasive Streptococcus pneumoniae, UZ Leuven, Leuven, Belgium
| | - Stefanie Desmet
- Laboratory of Clinical Microbiology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- National Reference Centre for invasive Streptococcus pneumoniae, UZ Leuven, Leuven, Belgium
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8
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King LM, Andrejko KL, Kabbani S, Tartof SY, Hicks LA, Cohen AL, Kobayashi M, Lewnard JA. Outpatient Visits and Antibiotic Use Due to Higher-Valency Pneumococcal Vaccine Serotypes. J Infect Dis 2024; 230:821-831. [PMID: 38498565 PMCID: PMC11481348 DOI: 10.1093/infdis/jiae142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 02/19/2024] [Accepted: 03/14/2024] [Indexed: 03/20/2024] Open
Abstract
BACKGROUND In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in US children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts. METHODS We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national health care surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses. RESULTS Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval, 1.8-3.9) visits and 2.4 (95% CI, 1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (95% CI, 11.2-20.4) visits and 13.2 (95% CI, 9.9-18.0) antibiotic prescriptions annually per 1000 children. PCV15/20-additional serotypes account for 0.4% (95% CI, 0.2%-0.6%) and 2.1% (95% CI, 1.5%-3.0%) of pediatric outpatient antibiotic use. CONCLUSIONS Compared with PCV15-additional serotypes, PCV20-additional serotypes account for > 5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use.
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Affiliation(s)
- Laura M King
- School of Public Health, University of California, Berkeley, California, USA
| | - Kristin L Andrejko
- Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Sarah Kabbani
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Sara Y Tartof
- Department of Research and Evaluation, Southern California, Kaiser Permanente, Pasadena, California, USA
| | - Lauri A Hicks
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Adam L Cohen
- Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Miwako Kobayashi
- Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Joseph A Lewnard
- School of Public Health, University of California, Berkeley, California, USA
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9
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Meng T, James B, Haymore J, Wang R, Gubler S, Taylor SA, Finn MG, Teyton L, Deng S, Savage PB. Synthesis of propargyl glycosides of Streptococcus pneumoniae serotypes 6A and 6B for glycoconjugate vaccines. Tetrahedron 2024; 165:134186. [PMID: 39280115 PMCID: PMC11391900 DOI: 10.1016/j.tet.2024.134186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/18/2024]
Abstract
We developed a method for making immune responses to bacterial glycans T cell-dependent, which involves attachment of short, synthetic glycans to a virus-like nanoparticle (VLP). This strategy enhances immune responses to glycans by facilitating cognate T cell help of B cells, leading to antibody class switching and affinity maturation yielding high-affinity, anti-glycan antibodies. This method requires synthesis of bacterial glycans as propargyl glycosides for covalent attachment to VLPs, and the resulting short linker between the VLP and glycan is important for optimal T cell receptor recognition. In this work, glycans that are part of the capsular polysaccharides (CPS) produced by Streptococcus pneumoniae serotypes Sp6A and Sp6B were synthesized as disaccharides and trisaccharides. The optimal glycan epitope for antibody binding to the CPS from these serotypes is unknown, and differing "frames" of disaccharides and trisaccharides were prepared to elucidate the optimal antigen for antibody binding.
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Affiliation(s)
- Tianyao Meng
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA
| | - Brady James
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA
| | - Jared Haymore
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA
| | - Rui Wang
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA
| | - Shawn Gubler
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA
| | - Seth A Taylor
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA
- School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA
| | - M G Finn
- School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA
| | - Luc Teyton
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
| | - Shenglou Deng
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA
| | - Paul B Savage
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA
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Dalmieda J, Hitchcock M, Xu J. High diversity within and low but significant genetic differentiation among geographic and temporal populations of the global Streptococcus pneumoniae. Can J Microbiol 2024; 70:226-237. [PMID: 38422492 DOI: 10.1139/cjm-2023-0155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2024]
Abstract
Streptococcus pneumoniae is the major cause of invasive pneumococcal disease. However, the global population structure remains largely unexplored. In this study, we investigated the spatial and temporal patterns of genetic variation of S. pneumoniae based on archived multilocus sequence typing data from PubMLST.org. Our analyses demonstrated both shared and unique distributions of sequence types (STs) and allele types among regional populations. Among the 17 915 global STs, 36 representing 15 263 isolates were broadly shared among all six continents, consistent with recent clonal dispersal and expansion of this pathogen. The analysis of molecular variance revealed that >96% genetic variations were found within individual regional populations. However, though low (<4%), statistically significant genetic differentiation among regional populations was observed. Comparisons between non-clone-corrected and clone-corrected datasets showed that localized clonal expansion contributed significantly to the observed genetic differentiations among regions. Temporal analyses of the isolates showed that implementation of pneumococcal conjugate vaccine impacted the distributions of STs, but the effect on population structure was relatively limited. Linkage disequilibrium analyses identified evidence for recombination in all continental populations; however, the inferred recombination was not random. We discussed the limitations and implications of our analyses to the global epidemiology and future vaccine developments for S. pneumoniae.
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Affiliation(s)
- Jezreel Dalmieda
- Department of Biology, McMaster University, Hamilton, ON L8S 4K1, Canada
| | - Megan Hitchcock
- Department of Biology, McMaster University, Hamilton, ON L8S 4K1, Canada
| | - Jianping Xu
- Department of Biology, McMaster University, Hamilton, ON L8S 4K1, Canada
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11
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Johnson CN, Wilde S, Tuomanen E, Rosch JW. Convergent impact of vaccination and antibiotic pressures on pneumococcal populations. Cell Chem Biol 2024; 31:195-206. [PMID: 38052216 PMCID: PMC10938186 DOI: 10.1016/j.chembiol.2023.11.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 09/08/2023] [Accepted: 11/07/2023] [Indexed: 12/07/2023]
Abstract
Streptococcus pneumoniae is a remarkably adaptable and successful human pathogen, playing dual roles of both asymptomatic carriage in the nasopharynx and invasive disease including pneumonia, bacteremia, and meningitis. Efficacious vaccines and effective antibiotic therapies are critical to mitigating morbidity and mortality. However, clinical interventions can be rapidly circumvented by the pneumococcus by its inherent proclivity for genetic exchange. This leads to an underappreciated interplay between vaccine and antibiotic pressures on pneumococcal populations. Circulating populations have undergone dramatic shifts due to the introduction of capsule-based vaccines of increasing valency imparting strong selective pressures. These alterations in population structure have concurrent consequences on the frequency of antibiotic resistance profiles in the population. This review will discuss the interactions of these two selective forces. Understanding and forecasting the drivers of antibiotic resistance and capsule switching are of critical importance for public health, particularly for such a genetically promiscuous pathogen as S. pneumoniae.
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Affiliation(s)
- Cydney N Johnson
- Department of Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Shyra Wilde
- Department of Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Elaine Tuomanen
- Department of Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
| | - Jason W Rosch
- Department of Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
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12
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King LM, Andrejko KL, Kabbani S, Tartof SY, Hicks LA, Cohen AL, Kobayashi M, Lewnard JA. Pediatric outpatient visits and antibiotic use attributable to higher valency pneumococcal conjugate vaccine serotypes. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.08.24.23294570. [PMID: 37662372 PMCID: PMC10473805 DOI: 10.1101/2023.08.24.23294570] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/05/2023]
Abstract
Importance Streptococcus pneumoniae is a known etiology of acute respiratory infections (ARIs), which account for large proportions of outpatient visits and antibiotic use in children. In 2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15, PCV20) were recommended for routine use in infants. However, the burden of outpatient healthcare utilization among U.S. children attributable to the additional, non-PCV13 serotypes in PCV15/20 is unknown. Objective To estimate the incidence of outpatient visits and antibiotic prescriptions in U.S. children for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional serotypes (non-PCV13 serotypes) to quantify potential impacts of PCV15/20 on outpatient visits and antibiotic prescriptions for these conditions. Design Multi-component study including descriptive analyses of cross-sectional and cohort data on outpatient visits and antibiotic prescriptions from 2016-2019 and meta-analyses of pneumococcal serotype distribution in non-invasive respiratory infections. Setting Outpatient visits and antibiotic prescriptions among U.S. children. Participants Pediatric visits and antibiotic prescriptions among children captured in the National Ambulatory Medical Care Survey (NAMCS), the National Hospital Ambulatory Medicare Care Survey (NHAMCS), and Merative MarketScan, collectively representing healthcare delivery across all outpatient settings. Incidence denominators estimated using census (NAMCS/NHAMCS) and enrollment (MarketScan) data. Main outcomes and measures Pediatric outpatient visit and antibiotic prescription incidence for acute otitis media, pneumonia, and sinusitis associated with PCV15/20-additional serotypes. Results We estimated that per 1000 children annually, PCV15-additional serotypes accounted for 2.7 (95% confidence interval 1.8-3.9) visits and 2.4 (1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (11.2-20.4) visits and 13.2 (9.9-18.0) antibiotic prescriptions annually per 1,000 children. Projected to national counts, PCV15/20-additional serotypes account for 173,000 (118,000-252,000) and 968,000 (722,000-1,318,000) antibiotic prescriptions among U.S. children each year, translating to 0.4% (0.2-0.6%) and 2.1% (1.5-3.0%) of all outpatient antibiotic use among children. Conclusions and relevance PCV15/20-additional serotypes account for a large burden of pediatric outpatient healthcare utilization. Compared with PCV15-additional serotypes, PCV20-additional serotypes account for >5 times the burden of visits and antibiotic prescriptions. These higher-valency PCVs, especially PCV20, may contribute to preventing ARIs and antibiotic use in children.
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Affiliation(s)
- Laura M King
- School of Public Health, University of California, Berkeley, Berkeley, CA
| | - Kristin L Andrejko
- Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, GA
| | - Sarah Kabbani
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, GA
| | - Sara Y Tartof
- Kaiser Permanente Department of Research & Evaluation Southern California, Pasadena, CA
| | - Lauri A Hicks
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, GA
| | - Adam L Cohen
- Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, GA
| | - Miwako Kobayashi
- Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, GA
| | - Joseph A Lewnard
- School of Public Health, University of California, Berkeley, Berkeley, CA
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13
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Lister AJJ, Dombay E, Cleary DW, Sulaiman LH, Clarke SC. A brief history of and future prospects for pneumococcal vaccination in Malaysia. Pneumonia (Nathan) 2023; 15:12. [PMID: 37620925 PMCID: PMC10463521 DOI: 10.1186/s41479-023-00114-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 07/30/2023] [Indexed: 08/26/2023] Open
Abstract
Pneumococcal pneumonia remains a significant global public health issue. Malaysia has recently added the 10 valent pneumococcal conjugate vaccine to its national immunisation programme. Data on pneumococcal serotype epidemiology is vital for informing national vaccination policy. However, there remains a lack of representative population-based pneumococcal surveillance in Malaysia to help both the assessment of vaccine effectiveness in the country and to shape future vaccine policy. This review explores the history of pneumococcal vaccination, the burden of pneumococcal disease in Malaysia, and offers an insight into the prospects for reducing pneumococcal disease in Malaysia.
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Affiliation(s)
- Alex J J Lister
- Faculty of Medicine, Institute for Life Sciences, University of Southampton, Southampton, UK
| | - Evelin Dombay
- Faculty of Medicine, Institute for Life Sciences, University of Southampton, Southampton, UK
| | - David W Cleary
- Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- NIHR Birmingham Biomedical Research Centre, Institute of Translational Medicine, Birmingham, Birmingham, UK
| | - Lokman H Sulaiman
- Centre for Environment and Population Health, Institute for Research, Development, and Innovation, International Medical University, Kuala Lumpur, Malaysia
- Department of Community Medicine, School of Medicine, International Medical University, Kuala Lumpur, Malaysia
| | - Stuart C Clarke
- Faculty of Medicine, Institute for Life Sciences, University of Southampton, Southampton, UK.
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Trust, Southampton, UK.
- Global Health Research Institute, University of Southampton, Southampton, UK.
- School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia.
- Centre for Translational Research, Institute for Research, Development, and Innovation, International Medical University, Kuala Lumpur, Malaysia.
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14
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Abu-Helalah M, Al-Mnayyis A, Alzoubi H, Al-Abdallah R, Jdaitawi H, Nafi O, Abu-Sal K, Altawalbeh A, Khlaifat A, Al-Zayadneh E, Almaaitah I, Borghol I, Batarseh F, Okkeh O, Dalal A, Alhendi A, Almaaitah M, Al-Lahham A, Gazo M, Abu Ekteish F, Elnasser Z. Epidemiology of Streptococcus pneumoniae Serotypes in Jordan Amongst Children Younger than the Age of 5: A National Cross-Sectional Study. Vaccines (Basel) 2023; 11:1396. [PMID: 37766074 PMCID: PMC10536609 DOI: 10.3390/vaccines11091396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/17/2023] [Accepted: 08/21/2023] [Indexed: 09/29/2023] Open
Abstract
INTRODUCTION Streptococcus pneumoniae infections are a major cause of mortality and morbidity worldwide. In Jordan, pneumococcal conjugate vaccines (PCVs) are not included in the national vaccination program. Due to the current availability of several PCVs, including PCV-10, PCV-13, and PCV-15, along with PCV-20, currently undergoing pediatric approvals globally, the decision to introduce PCVs and their selection should be based on valid local data on the common serotypes of Streptococcus pneumoniae. METHODS This cross-sectional study aimed to identify the frequency of serotypes of Streptococcus pneumoniae in children aged below 5 years hospitalized with invasive pneumococcal diseases (IPDs), including pneumonia, septicemia, and meningitis, during the study's duration in representative areas of Jordan. Serotyping for culture-positive cases was based on the capsular reaction test, known as the Quellung reaction. qPCR was conducted on the blood samples of patients with lobar pneumonia identified via X-ray or on cerebrospinal fluid for those with a positive latex agglutination test for Streptococcus pneumoniae. RESULTS This study was based on the analysis of the serotypes of 1015 Streptococcus pneumoniae cases among children younger than the age of 5: 1006 cases with pneumonia, 6 cases with meningitis, and 3 cases with septicemia. Only 23 culture-positive cases were identified in comparison to 992 lobar pneumonia cases, which were PCR-positive but culture-negative, with a PCR positivity rate of 92%. Serotypes 6B, 6A, 14, and 19F were the most common serotypes identified in this study, with prevalence rates of 16.45%, 13.60%, 12.12%, and 8.18%, respectively. PCV-10, PCV-13, PCV-15, and PCV-20 coverage rates were 45.32%, 61.87%, 64.14%, and 68.47%, respectively. DISCUSSION To the best of our knowledge, this is the largest prospective study from the Middle East and one of the largest studies worldwide showing the serotypes of Streptococcus pneumoniae. It reveals the urgency for the introduction of a PCV vaccination in Jordan, utilizing recently developed vaccines with a broader serotype coverage.
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Affiliation(s)
- Munir Abu-Helalah
- Department of Family and Community Medicine, Faculty of Medicine, Jordan University, Amman 11942, Jordan
| | - Asma’a Al-Mnayyis
- Department of Clinical Sciences, College of Medicine, Yarmouk University, Irbid 21163, Jordan;
| | - Hamed Alzoubi
- Department of Pathology and Microbiology, King Abdullah University Hospital, Jordan University of Science and Technology, Irbid 22110, Jordan; (H.A.); (Z.E.)
| | - Ruba Al-Abdallah
- Medical Department, MENA Center for Research & Development and Internship, Amman 11931, Jordan; (R.A.-A.); (F.B.); (O.O.); (A.D.); (A.A.)
| | - Hussein Jdaitawi
- Ministry of Health, Princess Rahma Pediatrics Hospital, Irbid 21163, Jordan;
| | - Omar Nafi
- Faculty of Medicine, Mutah University, Mutah 61110, Jordan;
| | - Kamel Abu-Sal
- Vaccines Department, Ministry of Health, Amman 11931, Jordan;
| | - Alaa Altawalbeh
- Royal Medical Services, Amman 1193, Jordan; (A.A.); (A.K.); (M.A.)
| | - Alia Khlaifat
- Royal Medical Services, Amman 1193, Jordan; (A.A.); (A.K.); (M.A.)
| | - Enas Al-Zayadneh
- Department of Pediatrics, Faculty of Medicine, Jordan University, Amman 11942, Jordan;
| | - Ihsan Almaaitah
- Pediatrics Department, Zarqa Governmental Hospital, Zarqa 13116, Jordan;
| | | | - Fadi Batarseh
- Medical Department, MENA Center for Research & Development and Internship, Amman 11931, Jordan; (R.A.-A.); (F.B.); (O.O.); (A.D.); (A.A.)
| | - Omar Okkeh
- Medical Department, MENA Center for Research & Development and Internship, Amman 11931, Jordan; (R.A.-A.); (F.B.); (O.O.); (A.D.); (A.A.)
| | - Abdallah Dalal
- Medical Department, MENA Center for Research & Development and Internship, Amman 11931, Jordan; (R.A.-A.); (F.B.); (O.O.); (A.D.); (A.A.)
| | - Ahmad Alhendi
- Medical Department, MENA Center for Research & Development and Internship, Amman 11931, Jordan; (R.A.-A.); (F.B.); (O.O.); (A.D.); (A.A.)
| | | | - Adnan Al-Lahham
- Department of Biomedical Engineering, School of Applied Medical Sciences, German-Jordanian University, Amman 11931, Jordan;
| | - Mahmoud Gazo
- Department of Central Laboratories, Ministry of Health, Amman 11931, Jordan
| | - Faisal Abu Ekteish
- Department of Pediatrics, Faculty of Medicine, King Abdullah University Hospital, Jordan University of Science and Technology, Irbid 22110, Jordan;
| | - Ziad Elnasser
- Department of Pathology and Microbiology, King Abdullah University Hospital, Jordan University of Science and Technology, Irbid 22110, Jordan; (H.A.); (Z.E.)
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Cedrone F, Montagna V, Del Duca L, Camplone L, Mazzocca R, Carfagnini F, Fortunato V, Di Martino G. The Burden of Streptococcus pneumoniae-Related Admissions and In-Hospital Mortality: A Retrospective Observational Study between the Years 2015 and 2022 from a Southern Italian Province. Vaccines (Basel) 2023; 11:1324. [PMID: 37631892 PMCID: PMC10458359 DOI: 10.3390/vaccines11081324] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 07/29/2023] [Accepted: 07/31/2023] [Indexed: 08/29/2023] Open
Abstract
Streptococcus pneumoniae (SP) has high worldwide incidence and related morbidity and mortality, particularly among children and geriatric patients. SP infection could manifest with pneumonia, bacteremia, sepsis, meningitis, and osteomyelitis. This was a retrospective study aimed at evaluating the incidence, comorbidities, and factors associated with in-hospital mortality of pneumococcal disease-related hospitalization in a province in southern Italy from the years 2015 to 2022. This study was performed in the Local Health Authority (LHA) of Pescara. Data were collected from hospital discharge records (HDRs): this database is composed of 288,110 discharge records from LHA Pescara's hospitals from 2015 to 2022. Streptococcus Pneumoniae-related hospitalizations were about 5% of the hospitalizations; 67% of these were without comorbidities; 21% were with one comorbidity; and 13% were with two or more comorbidities. Regarding mortality of SP infection, the most affected age group was older people, with the percentage of cases among the over-65s being more than 50% compared to the other age groups. HDRs represent a valid and useful epidemiological tool for evaluating the direct impact of pneumococcal disease on the population and also indirectly for evaluating the effectiveness of vaccination strategies and directing them.
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Affiliation(s)
- Fabrizio Cedrone
- Hospital Healthcare Management, Local Health Autority of Pescara, Via Renato Paolini, 65124 Pescara, Italy; (L.D.D.); (F.C.); (V.F.)
| | - Vincenzo Montagna
- Postgraduate School of Hygiene and Preventive Medicine, Università Politecnica delle Marche, 60100 Ancona, Italy;
| | - Livio Del Duca
- Hospital Healthcare Management, Local Health Autority of Pescara, Via Renato Paolini, 65124 Pescara, Italy; (L.D.D.); (F.C.); (V.F.)
| | - Laura Camplone
- Postgraduate School of Hygiene and Preventive Medicine, University of L’Aquila, 67100 L’Aquila, Italy; (L.C.); (R.M.)
| | - Riccardo Mazzocca
- Postgraduate School of Hygiene and Preventive Medicine, University of L’Aquila, 67100 L’Aquila, Italy; (L.C.); (R.M.)
| | - Federica Carfagnini
- Hospital Healthcare Management, Local Health Autority of Pescara, Via Renato Paolini, 65124 Pescara, Italy; (L.D.D.); (F.C.); (V.F.)
| | - Valterio Fortunato
- Hospital Healthcare Management, Local Health Autority of Pescara, Via Renato Paolini, 65124 Pescara, Italy; (L.D.D.); (F.C.); (V.F.)
| | - Giuseppe Di Martino
- Department of Medicine and Ageing Sciences, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy;
- Unit of Hygiene, Epidemiology and Public Health, Local Health Authority of Pescara, 65100 Pescara, Italy
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16
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Zane L, Kraschowetz S, Trentini MM, Alves VDS, Araujo SC, Goulart C, Leite LCDC, Gonçalves VM. Peptide linker increased the stability of pneumococcal fusion protein vaccine candidate. Front Bioeng Biotechnol 2023; 11:1108300. [PMID: 36777254 PMCID: PMC9909212 DOI: 10.3389/fbioe.2023.1108300] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 01/16/2023] [Indexed: 01/27/2023] Open
Abstract
Streptococcus pneumoniae is a bacterial pathogen exclusive to humans, responsible for respiratory and systemic diseases. Pneumococcal protein vaccines have been proposed as serotype-independent alternatives to currently used conjugated polysaccharide vaccines, which have presented limitations regarding their coverage. Previously in our group, pneumococcal surface protein A (PspA) and detoxified pneumolysin (PdT) were genetically fused and the hybrid protein protected mice against pneumococcal challenge, offered higher cross-protection against different strains and showed greater opsonophagocytosis rate than co-administered proteins. As juxtaposed fusion was unstable to upscale production of the protein, flexible (PspA-FL-PdT) and rigid (PspA-RL-PdT) molecular linkers were inserted between the antigens to increase stability. This work aimed to produce recombinant fusion proteins, evaluate their stability after linker insertion, both in silico and experimentally, and enable the production of two antigens in a single process. The two constructs with linkers were cloned into Escherichia coli and hybrid proteins were purified using chromatography; purity was evaluated by SDS-PAGE and stability by Western blot and high performance size exclusion chromatography. PspA-FL-PdT showed higher stability at -20°C and 4°C, without additional preservatives. In silico analyses also showed differences regarding stability of the fusion proteins, with molecule without linker presenting disallowed amino acid positions in Ramachandran plot and PspA-FL-PdT showing the best scores, in agreement with experimental results. Mice were immunized with three doses and different amounts of each protein. Both fusion proteins protected all groups of mice against intranasal lethal challenge. The results show the importance of hybrid protein structure on the stability of the products, which is essential for a successful bioprocess development.
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Affiliation(s)
- Luciano Zane
- Laboratory of Vaccine Development, Butantan Institute, Sao Paulo, Brazil,Interunits Graduate Program in Biotechnology, University of Sao Paulo, Sao Paulo, Brazil
| | - Stefanie Kraschowetz
- Laboratory of Vaccine Development, Butantan Institute, Sao Paulo, Brazil,Interunits Graduate Program in Biotechnology, University of Sao Paulo, Sao Paulo, Brazil
| | | | - Vitor dos Santos Alves
- Laboratory of Vaccine Development, Butantan Institute, Sao Paulo, Brazil,Interunits Graduate Program in Biotechnology, University of Sao Paulo, Sao Paulo, Brazil
| | - Sergio Carneiro Araujo
- Laboratory of Vaccine Development, Butantan Institute, Sao Paulo, Brazil,Interunits Graduate Program in Biotechnology, University of Sao Paulo, Sao Paulo, Brazil
| | - Cibelly Goulart
- Laboratory of Vaccine Development, Butantan Institute, Sao Paulo, Brazil,Interunits Graduate Program in Biotechnology, University of Sao Paulo, Sao Paulo, Brazil
| | | | - Viviane Maimoni Gonçalves
- Laboratory of Vaccine Development, Butantan Institute, Sao Paulo, Brazil,*Correspondence: Viviane Maimoni Gonçalves,
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17
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Interrogation of the contribution of (endo)lysin domains to tune their bacteriolytic efficiency provides a novel clue to design superior antibacterials. Int J Biol Macromol 2022; 223:1042-1053. [PMID: 36370862 DOI: 10.1016/j.ijbiomac.2022.11.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 11/04/2022] [Accepted: 11/05/2022] [Indexed: 11/11/2022]
Abstract
Bacteriophage-derived endolysins and bacterial autolysins (hereinafter lysins) represent a completely new class of efficient antibacterials. They prevent the development of bacterial resistance and help protect commensal microbiota, producing cell wall lysis. Here we have investigated whether the acquisition of enzymatic active domains (EADs) and cell wall binding domains (CWBDs) of balancing efficiencies could be a way of tuning natural lysin activity. The concept was applied to produce a chimeric lysin of superior antibacterial capacity using the endolysin Skl and the major pneumococcal autolysin LytA. Combination of the Skl EAD and the cell wall choline-binding domain (CBD) of LytA in the chimera QSLA increased the bacterial killing by 2 logs or more compared to parental enzymes at an equal concentration and extended the substrate range to resistant and emergent pneumococci and other pathogens of the mitis group. Contrarily, QLAS, containing LytA EAD and Skl CBD, was inactive against all tested strains, although domain structures were preserved and hydrolysis of purified cell walls maintained in both chimeras. As a whole, our study provides a novel clue to design superior lysins to fight multidrug-resistant pathogens based on domain selection, and a powerful in-vivo active lysin (QSLA) with promising therapeutic perspectives.
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18
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El‐Beyrouty C, Buckler R, Mitchell M, Phillips S, Groome S. Pneumococcal vaccination—A literature review and practice guideline update. Pharmacotherapy 2022; 42:724-740. [DOI: 10.1002/phar.2723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 06/21/2022] [Accepted: 06/27/2022] [Indexed: 11/08/2022]
Affiliation(s)
- Claudine El‐Beyrouty
- Department of Pharmacy Thomas Jefferson University Hospital Philadelphia Pennsylvania USA
| | - Rebecca Buckler
- Department of Pharmacy Thomas Jefferson University Hospital Philadelphia Pennsylvania USA
| | - Meghan Mitchell
- Department of Pharmacy Thomas Jefferson University Hospital Philadelphia Pennsylvania USA
| | - Samantha Phillips
- Department of Pharmacy Thomas Jefferson University Hospital Philadelphia Pennsylvania USA
| | - Sara Groome
- Department of Pharmacy Thomas Jefferson University Hospital Philadelphia Pennsylvania USA
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19
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Rajendar B, Janardhan Reddy MVN, Mulagalapati R, Patri S, Adusumilli M, Matur RV. High-Performance Anion-Exchange chromatography with conductivity detection method for simultaneous determination of nitrogen and phosphorus in polysaccharides. J Chromatogr B Analyt Technol Biomed Life Sci 2022; 1207:123367. [PMID: 35858510 DOI: 10.1016/j.jchromb.2022.123367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 06/16/2022] [Accepted: 07/10/2022] [Indexed: 10/17/2022]
Abstract
Capsular polysaccharides of Streptococcus pneumoniae contain a characteristic mix of monosaccharides in their structure resulting in immunologically distinct serotypes. Pneumococcal capsular polysaccharides include sugars such as hexoses, uronic acids, hexosamines, methyl pentoses, other functional groups are attached to the sugars are N and O-acetyl groups, nitrogen and phosphorus. Most of these components can be quantified using different colorimetric methods. However, available methods for quantifying nitrogen and phosphorus are not sensitive enough and laborious. We report a highly sensitive high-performance anion-exchange chromatography-conductivity detector (HPAEC-CD) method for quantifying nitrogen and phosphorus present in pneumococcal capsular polysaccharides. The method is reliable, robust and reproducible with no interference. The LOQ for nitrogen and phosphorus of 3.125 and 62.5 ng/mL, respectively, is highly critical for estimating low levels of total nitrogen and total phosphorus. We have implemented this method to quantify total nitrogen in Typhoid Vi polysaccharide and phosphorus in Haemophilus influenzae type-b polysaccharide. This method has greater application for quantification of nitrogen and phosphorus present in low concentrations in polysaccharide vaccines/biologicals.
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Affiliation(s)
- Burki Rajendar
- Research & Development, Biological E Limited, Shameerpet, Hyderabad 500078, India.
| | | | | | - Sumapriya Patri
- Research & Development, Biological E Limited, Shameerpet, Hyderabad 500078, India
| | - Madhavi Adusumilli
- Research & Development, Biological E Limited, Shameerpet, Hyderabad 500078, India
| | - Ramesh V Matur
- Research & Development, Biological E Limited, Shameerpet, Hyderabad 500078, India.
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20
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Mettu R, Lih YH, Vulupala HR, Chen CY, Hsu MH, Lo HJ, Liao KS, Cheng YY, Chiu CH, Wu CY. Synthetic Library of Oligosaccharides Derived from the Capsular Polysaccharide of Streptococcus pneumoniae Serotypes 6A and 6B and Their Immunological Studies. ACS Infect Dis 2022; 8:626-634. [PMID: 35171577 DOI: 10.1021/acsinfecdis.1c00646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Streptococcus pneumoniae serotypes 6A and 6B are two of the common causes of invasive pneumococcal diseases. Although capsular polysaccharide conjugates of these two serotypes are included in the leading 13-valent pneumococcal conjugate vaccine, its low immunogenicity and high threshold for manufacturing technology indicated the need for vaccine improvement. Structurally defined synthetic immunogens have potential in dealing with these problems. To this end, we built a library of capsular polysaccharide fragments through convergent chemical synthesis in [2 + 2], [4 + 4], [4 + 3], [4 + 2], and [4 + 1] coupling manners. The library is comprised of 18 glycan antigens from trisaccharides to pseudo-octasaccharides, derived from the capsular repeating phosphorylated pseudo-tetrasaccharide with or without phosphate. Eight of them were selected for mouse immunization and further immunological studies. Four pseudo-tetrasaccharides with terminal or bridging phosphate elicited opsonic antibodies, which exhibited bactericidal activities and moderate cross-reactivities.
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Affiliation(s)
- Ravinder Mettu
- Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan
| | - Yu-Hsuan Lih
- Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan
- Chemical Biology and Molecular Biophysics, Taiwan International Graduate Program, Academia Sinica, 128 Academia Road, Section 2,
Nankang, Taipei 11529, Taiwan
- Department of Chemistry, National Taiwan University, 1 Roosevelt Road, Section 4, Daan, Taipei 10617, Taiwan
| | - Hanmanth Reddy Vulupala
- Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan
| | - Chiang-Yun Chen
- Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan
| | - Mei-Hua Hsu
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 259 Wenhua first Road, Guishan, Taoyuan 33302, Taiwan
| | - Hong-Jay Lo
- Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan
| | - Kuo-Shiang Liao
- Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan
| | - Yang-Yu Cheng
- Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan
| | - Cheng-Hsun Chiu
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 259 Wenhua first Road, Guishan, Taoyuan 33302, Taiwan
| | - Chung-Yi Wu
- Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan
- Chemical Biology and Molecular Biophysics, Taiwan International Graduate Program, Academia Sinica, 128 Academia Road, Section 2,
Nankang, Taipei 11529, Taiwan
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21
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Nisar MI, Jehan F, Shahid S, Ahmed S, Shakoor S, Kabir F, Hotwani A, Muneer S, Khalid F, Muhammad S, Althouse BM, Hu H, Whitney CG, Ali A, Zaidi AKM, Omer SB, Iqbal N. Serotype-specific effectiveness against pneumococcal carriage and serotype replacement after ten-valent Pneumococcal Conjugate Vaccine (PCV10) introduction in Pakistan. PLoS One 2022; 17:e0262466. [PMID: 35061793 PMCID: PMC8782386 DOI: 10.1371/journal.pone.0262466] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 12/23/2021] [Indexed: 11/19/2022] Open
Abstract
Objective
Pakistan was one of the first South-Asian countries to introduce the ten-valent pneumococcal conjugate vaccine (PCV10) at the national level, using a 3+0 schedule without catchup, in 2013.
Methods
From 2014–18, fifteen children <2 years old were recruited every week in Matiari, Sindh, and nasopharyngeal swabs were collected. The samples were cultured, and pneumococcus was further serotyped through multiplex PCR at the Aga Khan University Hospital as per the method described by the Centers for Disease Control and Prevention, USA.
Results
Pneumococcus was detected in 2370/3140 (75%) children. Vaccine type (VT) and non-vaccine type (NVT) serotypes were carried by 379 and 1990 children. There was a significant decline in VT carriage (by 40.3%, p-value <0.001), whereas overall NVT carriage remained the same. The prevalence of VT serotypes 6B, 9V/9A, and 19F showed a significant decline by 58.8%, 79.3%, and 56%, respectively. The prevalence of NVT serotypes 19A, 21, and 10A increased by 70%, 33.3%, and 65.6%, respectively, whereas serotypes 13 and 9N/9L decreased by 53.4% and 51.8%, respectively. Serotype-specific vaccine effectiveness estimates that reached statistical significance were for 9V/9A (VE = 65.0, 95% CI 26.0–83.5%), 19F (VE = 55.3, 95% CI 15.5–76.4%) and for the vaccine related serotype 6A (VE = 28.4, 95% CI 0.9–48.2%).
Conclusion
The emergence of NVT serotypes, primarily 19A replacing VT serotypes in this rural community, necessitates continuous monitoring of serotypes in the carriage and invasive disease to evaluate the utility of existing vaccine formulations.
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Affiliation(s)
- Muhammad Imran Nisar
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
- * E-mail:
| | - Fyezah Jehan
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - Shahira Shahid
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - Sheraz Ahmed
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - Sadia Shakoor
- Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan
| | - Furqan Kabir
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - Aneeta Hotwani
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - Sahrish Muneer
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - Farah Khalid
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - Sajid Muhammad
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | | | - Hao Hu
- Bill & Melinda Gates Foundation, Seattle, WA, United States of America
| | | | - Asad Ali
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - Anita K. M. Zaidi
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
- Bill & Melinda Gates Foundation, Seattle, WA, United States of America
| | - Saad B. Omer
- Yale Institute for Global Health, New Haven, CT, United States of America
| | - Najeeha Iqbal
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
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22
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Sukhova EV, Yashunsky DV, Kurbatova EA, Akhmatova EA, Tsvetkov YE, Nifantiev NE. Synthesis and Preliminary Immunological Evaluation of a Pseudotetrasaccharide Related to a Repeating Unit of the Streptococcus pneumoniae Serotype 6A Capsular Polysaccharide. Front Mol Biosci 2021; 8:754753. [PMID: 34966778 PMCID: PMC8710661 DOI: 10.3389/fmolb.2021.754753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 10/29/2021] [Indexed: 11/21/2022] Open
Abstract
2-Aminoethyl glycoside of the pseudotetrasaccharide α-d-Glcp-(1→3)-α-l-Rhap-(1→3)-d-Rib-ol-(5-P-2)-α-d-Galp corresponding to a repeating unit of the Streptococcus pneumoniae type 6A capsular polysaccharide has been synthesized. A suitably protected pseudotrisaccharide α-d-Glcp-(1→3)-α-l-Rhap-(1→3)-d-Rib-ol with a free 5-OH group in the ribitol moiety and a 2-OH derivative of 2-trifluoroacetamidoethyl α-d-galactopyranoside have been efficiently prepared and then connected via a phosphate bridge using the hydrogen phosphonate procedure. Preliminary immunological evaluation of this pseudotetrasaccharide and the previously synthesized pseudotetrasaccharide corresponding to a repeating unit of the capsular polysaccharide of S. pneumoniae serotype 6B has shown that they contain epitopes specifically recognized by anti-serogroup 6 antibodies and are able to model well the corresponding capsular polysaccharides. Conjugates of the synthetic pseudotetrasaccharides with bovine serum albumin were shown to be immunogenic in mice.
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Affiliation(s)
- Elena V Sukhova
- Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
| | - Dmitry V Yashunsky
- Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
| | - Ekaterina A Kurbatova
- Laboratory of Therapeutic Vaccines, Mechnikov Research Institute for Vaccines and Sera, Moscow, Russia
| | - Elina A Akhmatova
- Laboratory of Therapeutic Vaccines, Mechnikov Research Institute for Vaccines and Sera, Moscow, Russia
| | - Yury E Tsvetkov
- Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
| | - Nikolay E Nifantiev
- Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
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23
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Ben Ayed N, Ktari S, Mezghani S, Mnif B, Mahjoubi F, Hammami A. Relationship Between Serotypes and Antimicrobial Nonsusceptibility of Streptococcus pneumoniae Clinical Isolates in Tunisia. Microb Drug Resist 2021; 28:370-377. [PMID: 34918966 DOI: 10.1089/mdr.2021.0266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Streptococcus pneumoniae remains a significant cause of morbidity and mortality worldwide despite the overall success of the vaccine programs. In Tunisia, pneumococcal conjugate vaccines (PCV)10 was introduced in the national immunization program in April 2019. We sought to determine the relationship between serotypes and antimicrobial nonsusceptibility of S. pneumoniae isolates recovered from clinical samples in the prevaccination period in the south of Tunisia. A total of 504 nonduplicate S. pneumoniae isolates collected between 2012 and 2018 were tested for antimicrobial susceptibility, among them 439 (87.1%) were serotyped. The most common serotypes were 19F (17.8%), 14 (15.3%), 3 (9.1%), 19A (8.2%), and 23F (7.3%). The proportions of isolates with serotypes covered by PCV7, PCV10, and PCV13 were 55.4%, 56.3%, and 77.9%, respectively. Three-quarters (74.4%) of pneumococcal isolates were nonsusceptible to penicillin, and about half (54.8%) were multidrug resistant. Penicillin nonsusceptibility was observed for all 19A and 23F isolates, and was significantly associated with serotypes 19F (odds ratio [OR]: 33.7) and 14 (OR: 8.7). A significant association with multidrug resistance was noted for serotypes 19A (OR: 10), 19F (OR: 9.4), 23F (OR: 8.6), and 6B (OR: 5.2). The alarming rates of pneumococcal antimicrobial nonsusceptibility and the strong association with the most prevalent serotypes compel microbiologists to monitor the impact of the PCV10 introduced recently in our national immunization program.
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Affiliation(s)
- Nourelhouda Ben Ayed
- Laboratory of Microbiology, Research Laboratory for Microorganisms and Human Disease, Habib Bourguiba University Hospital, University of Sfax, Sfax, Tunisia
- Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia
| | - Sonia Ktari
- Laboratory of Microbiology, Research Laboratory for Microorganisms and Human Disease, Habib Bourguiba University Hospital, University of Sfax, Sfax, Tunisia
- Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia
| | - Sonda Mezghani
- Laboratory of Microbiology, Research Laboratory for Microorganisms and Human Disease, Habib Bourguiba University Hospital, University of Sfax, Sfax, Tunisia
- Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia
| | - Basma Mnif
- Laboratory of Microbiology, Research Laboratory for Microorganisms and Human Disease, Habib Bourguiba University Hospital, University of Sfax, Sfax, Tunisia
- Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia
| | - Faouzia Mahjoubi
- Laboratory of Microbiology, Research Laboratory for Microorganisms and Human Disease, Habib Bourguiba University Hospital, University of Sfax, Sfax, Tunisia
- Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia
| | - Adnene Hammami
- Laboratory of Microbiology, Research Laboratory for Microorganisms and Human Disease, Habib Bourguiba University Hospital, University of Sfax, Sfax, Tunisia
- Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia
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24
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Mungall BA, Hoet B, Nieto Guevara J, Soumahoro L. A systematic review of invasive pneumococcal disease vaccine failures and breakthrough with higher-valency pneumococcal conjugate vaccines in children. Expert Rev Vaccines 2021; 21:201-214. [PMID: 34882050 DOI: 10.1080/14760584.2022.2012455] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
INTRODUCTION : The pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV or PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) protect against vaccine-serotype invasive pneumococcal disease (VT IPD). However, VT IPD can still occur in fully or partially vaccinated children (vaccine failure or breakthrough). We performed a systematic review of vaccine failures and breakthrough IPD with PCV10 and PCV13 in ≤5-year-olds. AREAS COVERED : We searched Scopus/Medline/EMBASE to retrieve articles/abstracts published between 1/2008-7/2019. We excluded reports from studies only including data from adults or children ≥6 years, exclusively assessing PCV7-vaccinated children or children with underlying comorbidities. Twenty-six reports (20 PCV13, 1 PCV10, 5 both), covering studies with various designs in six continents, using different schedules, were included. Collectively, these studies reported 469 VT IPD cases classified as vaccine failures and 403 as breakthrough. Vaccine failure and breakthrough rates were low: 8.4% and 9.3%, respectively, of all IPD in vaccinated children, consistent with the vaccines' high effectiveness. The main serotypes associated with vaccine failure or breakthrough were 19A, 3 and 19F in PCV13 studies and 14, 6B and vaccine-related 19A and 6A in PCV10 studies. EXPERT OPINION : As we move to vaccines with more serotypes, it is not only important to consider which serotypes are added, but also to monitor and address incomplete protection against specific serotypes.
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25
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Andrejko K, Ratnasiri B, Hausdorff WP, Laxminarayan R, Lewnard JA. Antimicrobial resistance in paediatric Streptococcus pneumoniae isolates amid global implementation of pneumococcal conjugate vaccines: a systematic review and meta-regression analysis. THE LANCET. MICROBE 2021; 2:e450-e460. [PMID: 34485957 PMCID: PMC8410609 DOI: 10.1016/s2666-5247(21)00064-1] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
BACKGROUND Pneumococcal diseases are a leading cause of morbidity and mortality among children globally, and the burden of these diseases might be worsened by antimicrobial resistance. To understand the effect of pneumococcal conjugate vaccine (PCV) deployment on antimicrobial resistance in pneumococci, we assessed the susceptibility of paediatric pneumococcal isolates to various antimicrobial drugs before and after PCV implementation. METHODS We did a systematic review of studies reporting antimicrobial susceptibility profiles of paediatric pneumococcal isolates between 2000 and 2020 using PubMed and the Antimicrobial Testing Leadership and Surveillance database (ATLAS; Pfizer). Population-based studies of invasive pneumococcal disease or nasopharyngeal colonisation were eligible for inclusion. As primary outcome measures, we extracted the proportions of isolates that were non-susceptible or resistant to penicillin, macrolides, sulfamethoxazole-trimethoprim, third-generation cephalosporins, and tetracycline from each study. Where available, we also extracted data on pneumococcal serotypes. We estimated changes in the proportion of isolates with reduced susceptibility or resistance to each antibiotic class using random-effects meta-regression models, adjusting for study-level and region-level heterogeneity, as well as secular trends, invasive or colonising isolate source, and countries' per-capita gross domestic product. FINDINGS From 4910 studies screened for inclusion, we extracted data from 559 studies on 312 783 paediatric isolates. Susceptibility of isolates varied substantially across regions both before and after implementation of any PCV product. On average across all regions, we estimated significant absolute reductions in the proportions of pneumococci showing non-susceptibility to penicillin (11·5%, 95% CI 8·6-14·4), sulfamethoxazole-trimethoprim (9·7%, 4·3-15·2), and third-generation cephalosporins (7·5%, 3·1-11·9), over the 10 years after implementation of any PCV product, and absolute reductions in the proportions of pneumococci resistant to penicillin (7·3%, 5·3-9·4), sulfamethoxazole-trimethoprim (16·0%, 11·0-21·2), third-generation cephalosporins (4·5%, 0·3-8·7), macrolides (3·6%, 0·7-6·6) and tetracycline (2·0%, 0·3-3·7). We did not find evidence of changes in the proportion of isolates non-susceptible to macrolides or tetracycline after PCV implementation. Observed changes in penicillin non-susceptibility were driven, in part, by replacement of vaccine-targeted serotypes with non-vaccine serotypes that were less likely to be non-susceptible. INTERPRETATION Implementation of PCVs has reduced the proportion of circulating pneumococci resistant to first-line antibiotic treatments for pneumonia. This effect merits consideration in assessments of vaccine impact and investments in coverage improvements. FUNDING Bill & Melinda Gates Foundation.
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Affiliation(s)
- Kristin Andrejko
- Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA
| | - Buddhika Ratnasiri
- College of Letters and Science, University of California, Berkeley, CA, USA
| | - William P Hausdorff
- PATH, Washington, DC, USA
- Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium
| | - Ramanan Laxminarayan
- Center for Disease Dynamics, Economics and Policy, New Delhi, India
- High Meadows Environmental Institute, Princeton University, Princeton, NJ, USA
| | - Joseph A Lewnard
- Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, USA
- Center for Computational Biology, College of Engineering, University of California, Berkeley, CA, USA
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26
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Wyllie AL, Warren JL, Regev-Yochay G, Givon-Lavi N, Dagan R, Weinberger DM. Serotype Patterns of Pneumococcal Disease in Adults Are Correlated With Carriage Patterns in Older Children. Clin Infect Dis 2021; 72:e768-e775. [PMID: 32989457 DOI: 10.1093/cid/ciaa1480] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND The importance of specific serotypes causing invasive pneumococcal disease (IPD) differs by age. Data on pneumococcal carriage in different age groups, along with data on serotype-specific invasiveness, could help explain these age-related patterns and their implications for vaccination. METHODS Using pneumococcal carriage and disease data from Israel, we evaluated the association between serotype-specific IPD in adults and serotype-specific carriage prevalence among children in different age categories, while adjusting for serotype-specific invasiveness. We estimated carriage prevalence using different age groupings that were selected a priori. The Deviance Information Criterion was used to determine which age groupings of carriage data best fit the adult IPD data. Serotype-specific disease patterns were further evaluated by stratifying IPD data by comorbidity status. RESULTS The relative frequency of serotypes causing IPD differed between adults and children, and also differed between older and younger adults and between adults with and without comorbidities. Serotypes overrepresented as causes of IPD in adults were more commonly carried in older children compared with younger children. In line with this, the serotype-specific frequency of carriage in older children, rather than infants, best correlated with serotype-specific IPD in adults. CONCLUSIONS These analyses demonstrate that the serotype patterns in carriage in older children, rather than infants, are best correlated with disease patterns in adults. This might suggest these older children are more influential for disease patterns in adults. These insights could help in optimizing vaccination strategies to reduce disease burden across all ages.
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Affiliation(s)
- Anne L Wyllie
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA
| | - Joshua L Warren
- Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA
| | - Gili Regev-Yochay
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Gertner Institute, Tel-Hashomer, Israel.,Infectious Diseases Unit, Sheba Medical Center, Tel-Hashomer, Israel
| | - Noga Givon-Lavi
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er Sheva, Israel
| | - Ron Dagan
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er Sheva, Israel
| | - Daniel M Weinberger
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA
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A Structural Model for the Ligand Binding of Pneumococcal Serotype 3 Capsular Polysaccharide-Specific Protective Antibodies. mBio 2021; 12:e0080021. [PMID: 34061603 PMCID: PMC8262990 DOI: 10.1128/mbio.00800-21] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Capsular polysaccharides (CPSs) are major virulence factors that decorate the surfaces of many human bacterial pathogens. In their pure form or as glycoconjugate vaccines, CPSs are extensively used in vaccines deployed in clinical practice worldwide. However, our understanding of the structural requirements for interactions between CPSs and antibodies is limited. A longstanding model based on comprehensive observations of antibody repertoires binding to CPSs is that antibodies expressing heavy chain variable gene family 3 (VH3) predominate in these binding interactions in humans and VH3 homologs in mice. Toward understanding this highly conserved interaction, we generated a panel of mouse monoclonal antibodies (MAb) against Streptococcus pneumoniae serotype 3 CPS, determined an X-ray crystal structure of a protective MAb in complex with a hexasaccharide derived from enzymatic hydrolysis of the polysaccharide, and elucidated the structural requirements for this binding interaction. The crystal structure revealed a binding pocket containing aromatic side chains, suggesting the importance of hydrophobicity in the interaction. Through mutational analysis, we determined the amino acids that are critical in carbohydrate binding. Through elucidating the structural and functional properties of a panel of murine MAbs, we offer an explanation for the predominant use of the human VH3 gene family in antibodies against CPSs with implications in knowledge-based vaccine design.
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28
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Cohen R, Levy C, Ouldali N, Goldrey M, Béchet S, Bonacorsi S, Varon E. Invasive Disease Potential of Pneumococcal Serotypes in Children After PCV13 Implementation. Clin Infect Dis 2021; 72:1453-1456. [PMID: 32804200 DOI: 10.1093/cid/ciaa917] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 06/26/2020] [Indexed: 01/08/2023] Open
Abstract
We aimed to assess the invasive disease potential of non-PCV13 serotypes after the implementation of this vaccine. Most non-PCV13 serotypes had low invasive disease potential. Among serotypes with the highest invasive disease potential (12F, 24F, 38, 8, 33F, 22F, and 10A), all but 24F and 38 were included in PCV20.
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Affiliation(s)
- Robert Cohen
- Association Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France.,Groupe de Pathologie Infectieuse Pédiatrique, Paris, France.,Unité Court Séjour, Petits Nourrissons, Service de Néonatalogie, Centre Hospitalier Intercommunal de Créteil, Créteil, France.,Université Paris Est, IMRB-GRC GEMINI, Créteil, France.,Clinical Research Center, Centre Hospitalier Intercommunal de Créteil, Créteil, France
| | - Corinne Levy
- Association Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France.,Groupe de Pathologie Infectieuse Pédiatrique, Paris, France.,Université Paris Est, IMRB-GRC GEMINI, Créteil, France.,Clinical Research Center, Centre Hospitalier Intercommunal de Créteil, Créteil, France
| | - Naim Ouldali
- Association Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France.,Groupe de Pathologie Infectieuse Pédiatrique, Paris, France.,Unité d'Epidémiologie Clinique, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, ECEVE INSERM UMR 1123, Paris, France
| | - Marie Goldrey
- Association Française de Pédiatrie Ambulatoire, Saint-Germain-en-Laye, France
| | - Stéphane Béchet
- Association Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France
| | - Stéphane Bonacorsi
- Université Paris Diderot, Sorbonne Paris Cité, France.,Service de Microbiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Robert-Debré, Paris, France
| | - Emmanuelle Varon
- Groupe de Pathologie Infectieuse Pédiatrique, Paris, France.,National Reference Center for Pneumococci, Centre Hospitalier Intercommunal de Créteil, Créteil, France
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29
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Bentley SD, Lo SW. Global genomic pathogen surveillance to inform vaccine strategies: a decade-long expedition in pneumococcal genomics. Genome Med 2021; 13:84. [PMID: 34001237 PMCID: PMC8130287 DOI: 10.1186/s13073-021-00901-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 04/30/2021] [Indexed: 11/10/2022] Open
Abstract
Vaccines are powerful agents in infectious disease prevention but often designed to protect against some strains that are most likely to spread and cause diseases. Most vaccines do not succeed in eradicating the pathogen and thus allow the potential emergence of vaccine evading strains. As with most evolutionary processes, being able to capture all variations across the entire genome gives us the best chance of monitoring and understanding the processes of vaccine evasion. Genomics is being widely adopted as the optimum approach for pathogen surveillance with the potential for early and precise identification of high-risk strains. Given sufficient longitudinal data, genomics also has the potential to forecast the emergence of such strains enabling immediate or pre-emptive intervention. In this review, we consider the strengths and challenges for pathogen genomic surveillance using the experience of the Global Pneumococcal Sequencing (GPS) project as an early example. We highlight the multifaceted nature of genome data and recent advances in genome-based tools to extract useful information relevant to inform vaccine strategies and treatment options. We conclude with future perspectives for genomic pathogen surveillance.
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Affiliation(s)
- Stephen D Bentley
- Parasites and Microbes, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
| | - Stephanie W Lo
- Parasites and Microbes, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK
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30
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Synthesis and delivery of Streptococcus pneumoniae capsular polysaccharides by recombinant attenuated Salmonella vaccines. Proc Natl Acad Sci U S A 2021; 118:2013350118. [PMID: 33380455 PMCID: PMC7812815 DOI: 10.1073/pnas.2013350118] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Pneumococcal infection-caused diseases are responsible for substantial morbidity and mortality worldwide. Traditional pneumococcal vaccines are developed based on purified capsular polysaccharides (CPS) or CPS conjugated to a protein carrier. Production processes of the traditional vaccines are laborious, and thereby increase the vaccine cost and limit their use in developing nations. A cost-effective pneumococcal vaccine using the recombinant attenuated Salmonella vaccine (RASV) was developed in this study. We cloned and expressed genes for seven serotypes of CPSs in the RASV strain. The RASV-delivered CPSs induced robust humoral and cell-mediated responses and mediated efficient protection of mice against pneumococcal infection. Our work provides an innovative strategy for mass producing low-cost bioconjugated polysaccharide vaccines for needle-free mucosal delivery against pneumococcal infections. Streptococcus pneumoniae capsular polysaccharides (CPSs) are major determinants of bacterial pathogenicity. CPSs of different serotypes form the main components of the pneumococcal vaccines Pneumovax, Prevnar7, and Prevnar13, which substantially reduced the S. pneumoniae disease burden in developed countries. However, the laborious production processes of traditional polysaccharide-based vaccines have raised the cost of the vaccines and limited their impact in developing countries. The aim of this study is to develop a kind of low-cost live vaccine based on using the recombinant attenuated Salmonella vaccine (RASV) system to protect against pneumococcal infections. We cloned genes for seven different serotypes of CPSs to be expressed by the RASV strain. Oral immunization of mice with the RASV-CPS strains elicited robust Th1 biased adaptive immune responses. All the CPS-specific antisera mediated opsonophagocytic killing of the corresponding serotype of S. pneumoniae in vitro. The RASV-CPS2 and RASV-CPS3 strains provided efficient protection of mice against challenge infections with either S. pneumoniae strain D39 or WU2. Synthesis and delivery of S. pneumoniae CPSs using the RASV strains provide an innovative strategy for low-cost pneumococcal vaccine development, production, and use.
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31
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Prevalence and Antimicrobial Susceptibility of Streptococcus pneumoniae Isolated from Clinical Samples in the Past 8 Years in Korea. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6615334. [PMID: 33997025 PMCID: PMC8099532 DOI: 10.1155/2021/6615334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 04/10/2021] [Accepted: 04/17/2021] [Indexed: 11/18/2022]
Abstract
Pneumococcal infection is the main causative agent of pneumonia, meningitis, and sepsis in immunocompromised and elderly people. The samples in this study were collected from subjects in an 800-bed hospital in Chungnam province, Korea, over the past 8 years. Of the 473,230 samples obtained for microbial culture from 2012 to 2019, Streptococcus pneumoniae was isolated from 714 samples collected from 702 patients, with a pneumococcal-positive rate of 0.15%. We investigated the temporal, demographic, and specimen-specific distributions, as well as the antibiotic susceptibility pattern for S. pneumonia. The age of patients ranged from 0 days to 98 years, with an average age of 64.7 years. The distribution among the sexes was 2.4 : 1 (male : female), with more samples isolated from male patients. We observed that spring was the predominant season in which the infection occurred, accounting for 37.6% of the cases. Pneumococci were most frequently isolated from sputum (608 cases, 85.2%). Invasive infections were detected at a rate of 66% (in blood cultures), and noninvasive infections were detected at a rate of 91% (in sputum cultures). Antimicrobial resistance to ceftriaxone, cefotaxime, erythromycin, tetracycline, clindamycin, cotrimoxazole, levofloxacin, and penicillin, based on noninvasive infections, was observed in 21.6%, 27.2%, 79.2%, 73.2%, 68.0%, 51.3%, 9.8%, and 18.1% of cases, respectively. Additionally, on average, 66.9% of multidrug-resistant bacteria showed resistance to three or more antimicrobial agents, and 2.8% showed resistance to all other antibacterial agents except vancomycin. These results might facilitate the administration of appropriate empirical antibacterial therapy for pneumococcal infections.
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32
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Dietl B, Henares D, Boix-Palop L, Muñoz-Almagro C, Garau J, Calbo E. Related Factors to Streptococcus pneumoniae Invasive Infection and Clinical Manifestations: The Potential Role of Nasopharyngeal Microbiome. Front Med (Lausanne) 2021; 8:650271. [PMID: 33996857 PMCID: PMC8117960 DOI: 10.3389/fmed.2021.650271] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 03/22/2021] [Indexed: 12/15/2022] Open
Abstract
Infections of the lower respiratory tract, such as pneumonia, are one of the leading causes of death worldwide. Streptococcus pneumoniae might colonize the upper respiratory tract and is the main aetiological agent of community-acquired pneumonia (CAP). In the last decades, several factors related to the host, the microorganism and the antibiotic therapy have been investigated to identify risk factors associated with the development of invasive pneumococcal disease (IPD). Nevertheless, these factors themselves do not explain the risk of developing disease or its severity. Recently, some studies have focused on the importance of nasopharyngeal (NP) microbiome and its relation to respiratory health. This review presents existing evidence of the potential role of NP microbiome in the development of IPD.
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Affiliation(s)
- Beatriz Dietl
- Infectious Diseases Unit, Hospital Universitari Mútua Terrassa, Terrassa, Spain
- Department of Medicine, Universitat Internacional de Catalunya, Barcelona, Spain
| | - Desirée Henares
- Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
- Center for Epidemiology and Public Health, CIBERESP, Instituto de Salud Carlos III, Madrid, Spain
| | - Lucía Boix-Palop
- Infectious Diseases Unit, Hospital Universitari Mútua Terrassa, Terrassa, Spain
- Department of Medicine, Universitat Internacional de Catalunya, Barcelona, Spain
| | - Carmen Muñoz-Almagro
- Department of Medicine, Universitat Internacional de Catalunya, Barcelona, Spain
- Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
- Center for Epidemiology and Public Health, CIBERESP, Instituto de Salud Carlos III, Madrid, Spain
| | - Javier Garau
- Internal Medicine Department, Clínica Rotger, Palma de Mallorca, Spain
| | - Esther Calbo
- Infectious Diseases Unit, Hospital Universitari Mútua Terrassa, Terrassa, Spain
- Department of Medicine, Universitat Internacional de Catalunya, Barcelona, Spain
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Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project. Microorganisms 2021; 9:microorganisms9040742. [PMID: 33918127 PMCID: PMC8066045 DOI: 10.3390/microorganisms9040742] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 03/25/2021] [Accepted: 03/26/2021] [Indexed: 12/27/2022] Open
Abstract
Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.
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Gening ML, Kurbatova EA, Nifantiev NE. Synthetic Analogs of Streptococcus pneumoniae Capsular Polysaccharides and Immunogenic Activities of Glycoconjugates. RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY 2021; 47:1-25. [PMID: 33776393 PMCID: PMC7980793 DOI: 10.1134/s1068162021010076] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 08/14/2020] [Accepted: 08/15/2020] [Indexed: 12/13/2022]
Abstract
Streptococcus pneumoniae is a Gram-positive bacterium (pneumococcus) that causes severe diseases in adults and children. It was established that some capsular polysaccharides of the clinically significant serotypes of S. pneumoniae in the composition of commercial pneumococcal polysaccharide or conjugate vaccines exhibit low immunogenicity. The review considers production methods and structural features of the synthetic oligosaccharides from the problematic pneumococcal serotypes that are characterized with low immunogenicity due to destruction or detrimental modification occurring in the process of their preparation and purification. Bacterial serotypes that cause severe pneumococcal diseases as well as serotypes not included in the composition of the pneumococcal conjugate vaccines are also discussed. It is demonstrated that the synthetic oligosaccharides corresponding to protective glycotopes of the capsular polysaccharides of various pneumococcal serotypes are capable of inducing formation of the protective opsonizing antibodies and immunological memory. Optimal constructs of oligosaccharides from the epidemiologically significant pneumococcal serotypes are presented that can be used for designing synthetic pneumococcal vaccines, as well as test systems for diagnosis of S. pneumoniae infections and monitoring of vaccination efficiency .
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Affiliation(s)
- M. L. Gening
- Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russia
| | - E A. Kurbatova
- Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, Russia
| | - N. E. Nifantiev
- Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russia
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Characterization of Blood-isolated, Penicillin-Nonsusceptible Streptococcus pneumoniae From Children Between 2014 and 2018 in Bojnurd, Iran. Jundishapur J Microbiol 2021. [DOI: 10.5812/jjm.111147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Streptococcus pneumoniae is one of the common bacterial pathogens in pediatrics. In this study, we performed antimicrobial susceptibility testing, serotyping, and molecular typing of blood-isolated strains of pneumococci in Bojnurd. Objectives: In the current study, blood-isolated, penicillin-nonsusceptible S. pneumoniae strains were subjected to antimicrobial susceptibility testing and typing of capsular polysaccharides using the quelling reaction and PCR method, as well as genotyping using the Multi Locus Sequence Typing (MLST) method. Methods: In this study, 51 S. pneumoniae strains were isolated from blood samples of children less than five-years-old in 2014 - 2018. Antibiogram was performed using the Kirby-Bauer method. All of the isolates were serotyped by the Quelling reaction and PCR. The MLST method was applied to determine the molecular types. Results: Our study revealed that the most common serotypes of blood-isolated pneumococci were 19A, 6A/B, 1, 23F, 19F, 14, 15B/C, and 15A, and the common serotypes in Penicillin-nonsusceptible pneumococci (PNSP) isolates were 19F, 19A, 23F, 14, and finally 15A, 6A/B, 1, and 15B/C. The MLST analysis of PNSP isolates revealed that three highly resistant isolates with MIC ≥ 16 belonged to Sweden15A-25-19A (ST63), Taiwan19F-14-1 (ST236), and Taiwan19F-14 (ST236) clones. Conclusions: Regarding the common serotypes in this study, it seems that PCV-13 is a suitable choice for vaccination in this area. We also observed a high prevalence of PNSP and multi-drug resistant (MDR) strains between 2014 and 2018. It seems that the Taiwan19F-14 clone and its related STs played an essential role in the diffusion of antibiotic-resistant S. pneumoniae isolates in Bojnurd.
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Izurieta P, Nieto Guevara J. Exploring the evidence behind the comparable impact of the pneumococcal conjugate vaccines PHiD-CV and PCV13 on overall pneumococcal disease. Hum Vaccin Immunother 2021; 18:1872341. [PMID: 33605846 PMCID: PMC8920200 DOI: 10.1080/21645515.2021.1872341] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
The worldwide implementation of pneumococcal conjugate vaccines (PCVs) in children has reduced the overall pneumococcal disease burden. Two PCVs are widely available for infant vaccination: the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) and the 13-valent PCV (PCV13). While these PCVs differ in serotype composition (PCV13 includes polysaccharides of serotypes 3, 6A and 19A; PHiD-CV does not), their impact on the overall pneumococcal disease burden in children is comparable. This commentary summarizes the evidence of comparability between PHiD-CV and PCV13 and explores why differences in serotype composition may not necessarily translate into a differential clinical impact. Both vaccines confer similarly high protection against disease caused by vaccine serotypes and lead to a partial replacement by non-vaccine serotypes. PHiD-CV does not protect against serotype 3 disease (not included in the vaccine) and PCV13’s effect on this serotype has been inconsistent. PHiD-CV provides some cross-protection against disease caused by vaccine-related serotype 19A but neither vaccine has fully controlled 19A disease. While protection against 19A is higher for PCV13 than PHiD-CV, replacement by non-PCV13 serotypes in settings with a PCV13 program appears to compensate for this difference. This results in a similar residual overall disease burden with both vaccines.
What is the context?
The pneumococcus bacterium can cause infections of the meninges, blood, lung, middle ear and sinuses. Two vaccins, Synflorix (GSK) and Prevnar 13 (Pfizer Inc.), are widely used to protect young children against these infections. The vaccines’ compositions differ: Synflorix includes antigens from 10 pneumococcus strains (or “serotypes”) and Prevnar 13 from 13 serotypes. However, both have a similar effect on the total pneumococcal disease burden in children.
What does this commentary highlight?
This commentary summarizes the evidence beihnd the two vaccines’ comparable impact on pneumococcal disase. It also looks at why the vaccines have a similar effect on the total pneumococcal disease burden despite their different compositions.
What is the impact on current thinking?
Given that Synflorix and Prevnar 13 have a comparable impact on pneumococcal disease, a country’s choice between the two vaccines will depend on vaccine supply, cost, logistical factors (e.g., transport, storage, training requirements of health workers) and the local pneumococcal epidemiology.
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Joshi SS, Al-Mamun MA, Weinberger DM. Correlates of Nonrandom Patterns of Serotype Switching in Pneumococcus. J Infect Dis 2021; 221:1669-1676. [PMID: 31875229 DOI: 10.1093/infdis/jiz687] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 12/23/2019] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Pneumococcus is a diverse pathogen, with >90 serotypes, each of which has a distinct polysaccharide capsule. Pneumococci can switch capsules, evading vaccine pressure. Certain serotype pairs are more likely to occur on the same genetic background as a results of serotype switching, but the drivers of these patterns are not well understood. METHODS We used the PubMLST and Global Pneumococcal Sequencing Project databases to quantify the number of genetic lineages on which different serotype pairs occur together. We also quantified the genetic diversity of each serotype. Regression model were used to evaluate the relationship between shared polysaccharide components and the frequency of serotype co-occurrence and diversity. RESULTS A number of serotype pairs occurred together on the same genetic lineage more commonly than expected. Co-occurrence of between-serogroup pairs was more common when both serotypes had glucose as a component of the capsule (and, potentially, glucuronic acid, any-N-acetylated sugar, or ribitol). Diversity also varied markedly by serotype and was associated with the presence of specific sugars in the capsule. CONCLUSIONS Certain pairs of serotypes are more likely to co-occur on the same genetic background. These patterns were correlated with shared polysaccharide components. This might reflect adaptation of strains to produce capsules with specific characteristics.
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Affiliation(s)
- Shreyas S Joshi
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA
| | - Mohammad A Al-Mamun
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA
| | - Daniel M Weinberger
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA
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Wangirapan A, Ayuthaya SIN, Katip W, Kasatpibal N, Mektrirat R, Anukool U, Oberdorfer P. Serotypes and Vaccine Coverage of Streptococcus Pneumoniae Colonization in the Nasopharynx of Thai Children in Congested Areas in Chiang Mai. Pathogens 2020; 9:pathogens9120988. [PMID: 33255981 PMCID: PMC7761239 DOI: 10.3390/pathogens9120988] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 11/21/2020] [Accepted: 11/23/2020] [Indexed: 11/16/2022] Open
Abstract
Streptococcus pneumoniae causes around 10% of all deaths in children younger than five years of age. This study aimed to examine the serogroups/serotypes of S. pneumoniae colonization and vaccine serotype coverage of this organism among Thai children. Nasopharyngeal swabs of children less than or equal to 15 years of age were obtained in congested areas in Chiang Mai from 1 February 2013 to 1 August 2013. The serotyping of S. pneumoniae isolates was performed using the ImmuLex™ kit and the vaccine serotype coverage for this organism was evaluated. A total of 292 children were enrolled. One hundred and thirty children (44.5%) had nasopharyngeal colonization with Streptococcus pneumoniae. Eighty-seven (66.9%) isolates were from children younger than five years of age, seventeen (13.1%) were from children aged 6-10 years, and twenty-six (20%) were from children aged 11-15 years. The five most common serogroups/serotypes isolated were 6 (6A, 6B, 6C) (46.1%), 23 (23F, 23A, 23B) (14.6%), 19 (19F, 19A, 19B, 19C) (8.5%), 15 (15F, 15A, 15B, 15C) (6.9%), and 14 (6.1%). Vaccine serotype coverages in pneumococcal conjugate vaccines (PCV):PCV7, PCV10, and PCV13 were 79.1%, 83.6%, and 85.9%, respectively. There were significant increases in coverage between PCV7 and PCV10 (from 79.1% to 83.6%, p < 0.001), PCV7 and PCV13 (from 79.1% to 85.9%, p < 0.001), and PCV10 and PCV13 (from 83.6% to 85.9%, p < 0.001). The majority of pneumococcal serogroup/serotype colonization in the nasopharynx of Thai children in the studied areas was included in the current licensed pneumococcal conjugated vaccines (PCVs). PCV vaccination should be considered for high-risk children to reduce the incidence of invasive pneumococcal disease among Thai children.
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Affiliation(s)
- Anchalee Wangirapan
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (A.W.); (S.I.n.A.)
| | - Satja Issaranggoon na Ayuthaya
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (A.W.); (S.I.n.A.)
| | - Wasan Katip
- Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
- Epidemiology Research Group of Infectious Disease (ERGID), Chiang Mai University, Chiang Mai 50200, Thailand; (N.K.); (R.M.); (U.A.)
- Correspondence: (W.K.); (P.O.); Tel.: +66-5394-4395 (W.K.)
| | - Nongyao Kasatpibal
- Epidemiology Research Group of Infectious Disease (ERGID), Chiang Mai University, Chiang Mai 50200, Thailand; (N.K.); (R.M.); (U.A.)
- Division of Nursing Science, Faculty of Nursing, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Raktham Mektrirat
- Epidemiology Research Group of Infectious Disease (ERGID), Chiang Mai University, Chiang Mai 50200, Thailand; (N.K.); (R.M.); (U.A.)
- Department of Veterinary Bioscience and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Usanee Anukool
- Epidemiology Research Group of Infectious Disease (ERGID), Chiang Mai University, Chiang Mai 50200, Thailand; (N.K.); (R.M.); (U.A.)
- Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Peninnah Oberdorfer
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (A.W.); (S.I.n.A.)
- Epidemiology Research Group of Infectious Disease (ERGID), Chiang Mai University, Chiang Mai 50200, Thailand; (N.K.); (R.M.); (U.A.)
- Correspondence: (W.K.); (P.O.); Tel.: +66-5394-4395 (W.K.)
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Lagousi T, Basdeki P, De Jonge MI, Spoulou V. Understanding host immune responses to pneumococcal proteins in the upper respiratory tract to develop serotype-independent pneumococcal vaccines. Expert Rev Vaccines 2020; 19:959-972. [PMID: 33107359 DOI: 10.1080/14760584.2020.1843433] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Introduction: Nasopharyngeal colonization is a precondition for mucosal and invasive pneumococcal disease. Prevention of colonization may reduce pneumococcal transmission and disease incidence. Therefore, several protein-based pneumococcal vaccines are currently under investigation. Areas covered: We aimed to better understand the host immune responses to pneumococcal proteins in the upper respiratory tract (URT) that could facilitate the development of serotype-independent pneumococcal vaccines. English peer-reviewed papers reporting immunological mechanisms involved in host immune response to pneumococcal proteins in the URT were retrieved through a PubMed search using the terms 'pneumococcal proteins,' 'nasopharyngeal colonization' and/or 'cellular/humoral host immune response.' Expert opinion: Although pneumococcal protein antigens induce humoral immune responses, as well as IL-17A-mediated immunity, none of them, when used as single antigen, is sufficient to control and broadly protect against pneumococcal colonization. Novel vaccines should contain multiple conserved protein antigens to activate both arms of the immune system and evoke protection against the whole spectrum of pneumococcal variants by reducing, rather than eradicating, pneumococcal carriage. The highest efficacy would likely be achieved when the vaccine is intranasally applied, inducing mucosal immunity and enhancing the first line of defense by restricting pneumococcal density in the URT, which in turn will lead to reduced transmission and protection against disease.
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Affiliation(s)
- Theano Lagousi
- First Department of Paediatrics, "Aghia Sophia" Children's Hospital, Immunobiology Research Laboratory and Infectious Diseases Department "MAKKA", Athens Medical School , Athens, Greece
| | - Paraskevi Basdeki
- First Department of Paediatrics, "Aghia Sophia" Children's Hospital, Immunobiology Research Laboratory and Infectious Diseases Department "MAKKA", Athens Medical School , Athens, Greece
| | - Marien I De Jonge
- Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences , Nijmegen, The Netherlands
| | - Vana Spoulou
- First Department of Paediatrics, "Aghia Sophia" Children's Hospital, Immunobiology Research Laboratory and Infectious Diseases Department "MAKKA", Athens Medical School , Athens, Greece
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Løchen A, Croucher NJ, Anderson RM. Divergent serotype replacement trends and increasing diversity in pneumococcal disease in high income settings reduce the benefit of expanding vaccine valency. Sci Rep 2020; 10:18977. [PMID: 33149149 PMCID: PMC7643077 DOI: 10.1038/s41598-020-75691-5] [Citation(s) in RCA: 99] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 10/08/2020] [Indexed: 11/25/2022] Open
Abstract
Streptococcus pneumoniae is a significant cause of otitis media, pneumonia, and meningitis. Only seven of the approximately 100 serotypes were initially included in the pneumococcal polysaccharide conjugate vaccine (PCV) in 2000 before it was expanded in subsequent years. Although the invasive pneumococcal disease (IPD) incidence due to vaccine serotypes (VT) has declined, partial replacement by non-vaccine serotypes (NVT) was observed following widespread vaccine uptake. We conducted a trend analysis assembling the available evidence for PCV impact on European, North American and Australian national IPD. Significant effectiveness against VT IPD in infants was observed, although the impact on national IPD incidence varied internationally due to serotype replacement. Currently, NVT serotypes 8, 9N, 15A and 23B are increasing in the countries assessed, although a variety of other NVTs are affecting each country and age group. Despite these common emerging serotypes, there has not been a dominant IPD serotype post-vaccination as there was pre-vaccination (serotype 14) or post-PCV7 (serotype 19A), suggesting that future vaccines with additional serotypes will be less effective at targeting and reducing IPD in global populations than previous PCVs. The rise of diverse NVTs in all settings’ top-ranked IPD-causing serotypes emphasizes the urgent need for surveillance data on serotype distribution and serotype-specific invasiveness post-vaccination to facilitate decision making concerning both expanding current vaccination programmes and increasing vaccine valency.
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Affiliation(s)
- Alessandra Løchen
- Department of Infectious Disease Epidemiology, School of Public Health, Imperial College, London, UK.,MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK
| | - Nicholas J Croucher
- Department of Infectious Disease Epidemiology, School of Public Health, Imperial College, London, UK. .,MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK.
| | - Roy M Anderson
- Department of Infectious Disease Epidemiology, School of Public Health, Imperial College, London, UK.,MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK
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41
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El-Kholy A, Badawy M, Gad M, Soliman M. Serotypes and Antimicrobial Susceptibility of Nasopharyngeal Isolates of Streptococcus pneumoniae from Children Less Than 5 Years Old in Egypt. Infect Drug Resist 2020; 13:3669-3677. [PMID: 33116686 PMCID: PMC7586055 DOI: 10.2147/idr.s250315] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 09/30/2020] [Indexed: 11/28/2022] Open
Abstract
Purpose Streptococcus pneumoniae (S. pneumoniae) is the etiology of severe and life-threatening infections in children less than 5 years old. Though pneumococcal conjugate vaccines (PCVs) are effective in the prevention of pneumococcal infections, yet they are not included in the National Immunization Program in Egypt pending the identification of pathogenic serotypes. As S. pneumoniae colonization of the pharynx predisposes to pneumonia and invasive pneumococcal disease (IPD) caused by the colonizing serotypes, identification of the nasopharyngeal (NP) serotypes can be a surrogate to the invasive serotypes. In this study, we aimed to 1. Identify the serotypes and antimicrobial susceptibility testing (AST) of Streptococcus pneumoniae colonizing the nasopharynx of Egyptian children younger than 5 years in two successive winter seasons. 2. Correlate the identified serotypes with vaccine coverage of the 13-valent conjugate pneumococcal vaccines (PCV13). 3. Compare the serotypes and AST of S. pneumoniae from NP to those of IPD that were routinely identified in our clinical laboratory during the study period. Materials and Methods The study was conducted in two successive winter seasons (December 2015–March 2016; December 2016–March 2017). We enrolled 334 children, aged 6 months to 5 years, attending the outpatient general clinics of Cairo University Children Hospital, excluding those with fever, signs of infection, history of antibiotic intake or hospitalization in the preceding month. We tested NP swabs for S. pneumoniae by culture and real-time PCR. Serotyping was performed by sequential multiplex PCR for all positive samples. AST was done to S. pneumoniae isolates by Vitek-2™ (BioMérieux, Marcy-L’Etoile, France). We included routinely detected S. pneumoniae from sterile body sites during the study period, and identified their serotypes and AST. Results PCR was positive for pneumococci in 217 out of 334 pharyngeal swabs (65%), including 186 typable samples. The most common serotypes were serotypes 1, 6ABC, 19 F, 5 and 18ABC. By culture, we isolated only 110 out of 334 pharyngeal swabs (32.9%). The theoretical coverage of the PCV13 vaccine for the detected serotypes was 77.4%. The AST of NP isolates revealed low susceptibility rates to all antimicrobials except for vancomycin, linezolid, levofloxacin and clindamycin. During the study period, we identified 40 IPD; 21 identified by PCR and 19 by culture. The commonest pneumococcal serotypes were 1, 18ABC, 6ABC and 5. The PCV13 coverage was 75%. By Vitek-2, the isolates showed 100%, 100%, 94.7%, 89.5%, 84.2%, 84.2% and 78.9% susceptibility to vancomycin, linezolid, clindamycin, levofloxacin, penicillin, cefotaxim and erythromycin, respectively. Conclusion Based on the serotype vaccine coverage and the emerging antimicrobial resistance of S. pneumoniae, PCVs will be valuable to Egyptian children.
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Affiliation(s)
- Amani El-Kholy
- Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Magda Badawy
- Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Maha Gad
- Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - May Soliman
- Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
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Panagiotou S, Chaguza C, Yahya R, Audshasai T, Baltazar M, Ressel L, Khandaker S, Alsahag M, Mitchell TJ, Prudhomme M, Kadioglu A, Yang M. Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity. Sci Rep 2020; 10:17313. [PMID: 33057054 PMCID: PMC7560715 DOI: 10.1038/s41598-020-73454-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 09/14/2020] [Indexed: 12/13/2022] Open
Abstract
Streptococcus pneumoniae is a devastating global pathogen. Prevalent in sub-Saharan Africa, pneumococcal serotype 1 is atypical in that it is rarely found as a nasopharyngeal coloniser, yet is described as one of the most common causes of invasive pneumococcal disease. Clonal sequence type (ST)-306 and ST615 are representative of the two major serotype 1 lineages A and C, respectively. Here we investigated the virulence properties and haemolytic activities of these 2 clonal types using in vivo mouse models and in vitro assays. A lethal dose of ST615 administered intranasally to mice led to the rapid onset of disease symptoms and resulted in 90% mortality. In contrast, mice exposed to the same infection dose of ST306 or a pneumolysin (Ply)-deficient ST615 failed to develop any disease symptoms. Interestingly, the 2 strains did not differ in their ability to bind the immune complement or to undergo neutrophil-mediated phagocytosis. Upon comparative genomic analysis, we found higher within-ST sequence diversity in ST615 compared with ST306 and determined that ZmpA, ZmpD proteins, and IgA protease, were uniquely found in ST615. Using cell fractionation and cell contact-dependent assay, we made the unexpected finding that ST615 harbours the expression of two haemolytic variants of Ply: a cell-wall restricted fully haemolytic Ply, and a cytosolic pool of Ply void of any detectable haemolytic activity. This is the first time such a phenomenon has been described. We discuss the biological significance of our observation in relation to the aptitude of the pneumococcus for sustaining its human reservoir.
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Affiliation(s)
- Stavros Panagiotou
- Department of Clinical Infection Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, The Ronald Ross Building, 8 West Derby St, Liverpool, L69 7BE, UK
| | - Chrispin Chaguza
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK
- Darwin College, University of Cambridge, Silver Street, Cambridge, CB3 9EU, UK
| | - Reham Yahya
- College of sciences and health professions, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
| | - Teerawit Audshasai
- Department of Clinical Infection Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, The Ronald Ross Building, 8 West Derby St, Liverpool, L69 7BE, UK
| | - Murielle Baltazar
- Department of Clinical Infection Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, The Ronald Ross Building, 8 West Derby St, Liverpool, L69 7BE, UK
| | - Lorenzo Ressel
- Department of Veterinary Pathology and Public Health, Institute of Veterinary Science, University of Liverpool, Leahurst Campus, Neston, CH64 7TE, UK
| | - Shadia Khandaker
- Department of Clinical Infection Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, The Ronald Ross Building, 8 West Derby St, Liverpool, L69 7BE, UK
| | - Mansoor Alsahag
- Department of Clinical Infection Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, The Ronald Ross Building, 8 West Derby St, Liverpool, L69 7BE, UK
- Faculty of Applied Medical Sciences, Albaha University, Albaha, Kingdom of Saudi Arabia
| | - Tim J Mitchell
- Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK
| | - Marc Prudhomme
- Université Paul Sabatier, Centre National de la Recherche Scientifique, 118 Route de Narbonne, 31062, Toulouse Cedex 9, France
| | - Aras Kadioglu
- Department of Clinical Infection Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, The Ronald Ross Building, 8 West Derby St, Liverpool, L69 7BE, UK.
| | - Marie Yang
- Department of Clinical Infection Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, The Ronald Ross Building, 8 West Derby St, Liverpool, L69 7BE, UK.
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Hanachi M, Kiran A, Cornick J, Harigua-Souiai E, Everett D, Benkahla A, Souiai O. Genomic Characteristics of Invasive Streptococcus pneumoniae Serotype 1 in New Caledonia Prior to the Introduction of PCV13. Bioinform Biol Insights 2020; 14:1177932220962106. [PMID: 33088176 PMCID: PMC7545519 DOI: 10.1177/1177932220962106] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 08/31/2020] [Indexed: 12/17/2022] Open
Abstract
Streptococcus pneumoniae serotype 1 is a common cause of global invasive pneumococcal disease. In New Caledonia, serotype 1 is the most prevalent serotype and led to two major outbreaks reported in the 2000s. The pneumococcal conjugate vaccine 13 (PCV13) was introduced into the vaccination routine, intending to prevent the expansion of serotype 1 in New Caledonia. Aiming to provide a baseline for monitoring the post-PCV13 changes, we performed a whole-genome sequence analysis on 67 serotype 1 isolates collected prior to the PCV13 introduction. To highlight the S. pneumoniae serotype 1 population structure, we performed a multilocus sequence typing (MLST) analysis revealing that NC serotype 1 consisted of 2 sequence types: ST3717 and the highly dominant ST306. Both sequence types harbored the same resistance genes to beta-lactams, macrolide, streptogramin B, fluoroquinolone, and lincosamide antibiotics. We have also identified 36 virulence genes that were ubiquitous to all the isolates. Among these virulence genes, the pneumolysin sequence presented an allelic profile associated with disease outbreaks and reduced hemolytic activity. Moreover, recombination hotspots were identified in 4 virulence genes and more notably in the cps locus (cps2L), potentially leading to capsular switching, a major mechanism of the emergence of nonvaccine types. In summary, this study represents the first overview of the genomic characteristics of S. pneumoniae serotype 1 in New Caledonia prior to the introduction of PCV13. This preliminary description represents a baseline to assess the impact of PCV13 on serotype 1 population structure and genomic diversity.
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Affiliation(s)
- Mariem Hanachi
- Laboratory of Bioinformatics, Biomathematics and Biostatistics-LR16IPT09, Institut Pasteur de Tunis, University of Tunis El Manar (UTM), Tunis, Tunisia.,Faculty of Science of Bizerte, University of Carthage, Jarzouna, Tunisia
| | - Anmol Kiran
- Queens Research Institute, University of Edinburgh, Edinburgh, UK.,Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
| | - Jennifer Cornick
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.,Departement of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK
| | - Emna Harigua-Souiai
- Laboratory of Molecular Epidemiology and Experimental Pathology-LR16IPT04, Institut Pasteur de Tunis, Université de Tunis El Manar, Tunis, Tunisia
| | - Dean Everett
- Queens Research Institute, University of Edinburgh, Edinburgh, UK.,Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
| | - Alia Benkahla
- Laboratory of Bioinformatics, Biomathematics and Biostatistics-LR16IPT09, Institut Pasteur de Tunis, University of Tunis El Manar (UTM), Tunis, Tunisia
| | - Oussama Souiai
- Laboratory of Bioinformatics, Biomathematics and Biostatistics-LR16IPT09, Institut Pasteur de Tunis, University of Tunis El Manar (UTM), Tunis, Tunisia.,Institut Supérieur des Technologies Médicales de Tunis, Université de Tunis El Manar, Tunis, Tunisia
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Seco BMS, Xu FF, Grafmüller A, Kottari N, Pereira CL, Seeberger PH. Sequential Linkage of Carbohydrate Antigens to Mimic Capsular Polysaccharides: Toward Semisynthetic Glycoconjugate Vaccine Candidates against Streptococcus pneumoniae Serotype 14. ACS Chem Biol 2020; 15:2395-2405. [PMID: 32835479 PMCID: PMC7506939 DOI: 10.1021/acschembio.0c00360] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
![]()
Vaccines
based on isolated polysaccharides successfully protect
humans from bacterial pathogens such as Streptococcus pneumoniae. Because polysaccharide production and isolation can be technically
challenging, glycoconjugates containing synthetic antigens are an
attractive alternative. Typically, the shortest possible oligosaccharide
antigen is preferable as syntheses of longer structures are more difficult
and time-consuming. Combining several protective epitopes or polysaccharide
repeating units as blocks by bonds other than glycosidic linkages
would greatly reduce the synthetic effort if the immunological response
to the polysaccharide could be retained. To explore this concept,
we bridged the well-understood and immunologically potent RU of S. pneumoniae serotype 14 (ST14) with an aliphatic spacer
and conjugated it to the carrier protein CRM197. Mice immunized with
the spacer-bridged glycan conjugates produced high levels of specific
antibodies after just one or two vaccine doses, while the tetrasaccharide
repeating unit alone required three doses. The antibodies recognized
specifically ST14 CPS, while no significant antibody levels were raised
against the spacer or unrelated CPS. Synthetic vaccines generated
antibodies with opsonic activity. Mimicking polysaccharides by coupling
repeating unit antigens via an aliphatic spacer may prove useful also
for the development of other glycoconjugate vaccine candidates, thereby
reducing the synthetic complexity while enhancing a faster immune
response.
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Affiliation(s)
- Bruna M. S. Seco
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany
- Department of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany
| | - Fei-Fei Xu
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany
- Department of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany
| | - Andrea Grafmüller
- Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany
| | - Naresh Kottari
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany
| | - Claney L. Pereira
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany
| | - Peter H. Seeberger
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany
- Department of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany
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Wu S, Guo X, Xu Z, Han M, Huang L, Tao Y, Li Y, Li Y, Zhang T, Bai Z. Early clinical predictors for the prognosis of invasive pneumococcal disease. BMC Infect Dis 2020; 20:651. [PMID: 32887563 PMCID: PMC7650274 DOI: 10.1186/s12879-020-05382-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 08/30/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Risk factors related to mortality due to invasive pneumococcal disease (IPD) have been unveiled previously, but early clinical manifestations of IPD based on prognosis remain uncovered. METHODS The demographic characteristics, clinical features, serotype, antibiotic susceptibility, and outcomes of 97 hospitalized children with laboratory-confirmed IPD from Suzhou, China, were collected and analyzed retrospectively. RESULTS The median age was 0.69 (0.49-1.55) years in the non-survivor group compared with 2.39 (0.90-3.81) years in the survivor group. The mortality of 97 children with laboratory-confirmed IPD was 17.5% (17/97), and 53.6% of them were aged less than 2 years. Pathogens were mainly from the blood and cerebrospinal fluid, and sepsis was the most frequent type. Statistically significant differences were found in hyperpyrexia, vomiting, anorexia, lethargy, poor perfusion of extremities, Hb level, and Plt count between the nonsurvival and survival groups. Further, the multivariate regression analysis showed that early signs, including hyperpyrexia, vomiting, anorexia, lethargy, and poor perfusion of extremities, were independent risk factors for the in-hospital mortality of children with laboratory-confirmed IPD. The mortality was also associated with antimicrobial sensitivity in pneumococcal isolates. The microbes in 1/17 (5.9%) children who were prescribed an antibiotic showed antimicrobial sensitivity in the nonsurvival group, compared with 21/80 (26.3%) children who survived. The most common serotypes identified were 6B (35.3%, 6/17), 14 (23.5%, 4/17), 19F (23.5%, 4/17), 19A (5.9%, 1/17), 23F (5.9%, 1/17), and 20 (5.9%, 1/17) in the nonsurvival group. The coverage of IPD serotypes of the 7-valent pneumococcal conjugate vaccine (PCV7) was 88.2% (15/17), while that of the 13-valent S. pneumoniae vaccine (PCV13) was 94.1% (16/17) of the coverage in the nonsurvival group. CONCLUSIONS Recurrent hyperpyrexia, vomiting, anorexia, lethargy, and poor perfusion of extremities in the early stage were independent predictors for the in-hospital mortality of children with laboratory-confirmed IPD. Appropriate use of antibiotics and PCV immunization were the keys to improve the outcome of IPD.
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Affiliation(s)
- Shuiyan Wu
- Pediatric Intensive Care Unit, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Xubei Guo
- Pediatric Intensive Care Unit, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Zhong Xu
- Pediatric Intensive Care Unit, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Meilin Han
- Pediatric Intensive Care Unit, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Lili Huang
- Laboratory department, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Yunzhen Tao
- Laboratory department, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Ying Li
- Pediatric Intensive Care Unit, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Yanhong Li
- Nephrology department, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Tao Zhang
- Key Laboratory of Public Health Safety, Ministry of Education-department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Zhenjiang Bai
- Pediatric Intensive Care Unit, Children's Hospital of Soochow University, Suzhou, Jiangsu, China.
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46
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Oliver MB, Swords WE. Comparative Analysis of Streptococcus pneumoniae Type I Restriction-Modification Loci: Variation in hsdS Gene Target Recognition Domains. Pathogens 2020; 9:pathogens9090712. [PMID: 32872494 PMCID: PMC7557576 DOI: 10.3390/pathogens9090712] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 08/21/2020] [Accepted: 08/25/2020] [Indexed: 11/17/2022] Open
Abstract
Streptococcus pneumoniae (pneumococcus) is a respiratory commensal pathogen that causes a range of infections, particularly in young children and the elderly. Pneumococci undergo spontaneous phase variation in colony opacity phenotype, in which DNA rearrangements within the Type I restriction-modification (R-M) system specificity gene hsdS can potentially generate up to six different hsdS alleles with differential DNA methylation activity, resulting in changes in gene expression. To gain a broader perspective of this system, we performed bioinformatic analyses of Type I R-M loci from 18 published pneumococcal genomes, and one R-M locus sequenced for this study, to compare genetic content, organization, and homology. All 19 loci encoded the genes hsdR, hsdM, hsdS, and at least one hsdS pseudogene, but differed in gene order, gene orientation, and hsdS target recognition domain (TRD) content. We determined the coding sequences of 87 hsdS TRDs and excluded seven from further analysis due to the presence of premature stop codons. Comparative analyses revealed that the TRD 1.1, 1.2, and 2.1 protein sequences had single amino acid substitutions, and TRD 2.2 and 2.3 each had seven differences. The results of this study indicate that variability exists among the gene content and arrangements within Type I R-M loci may provide an additional level of divergence between pneumococcal strains, such that phase variation-mediated control of virulence factors may vary significantly between individual strains. These findings are consistent with presently available transcript profile data.
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Affiliation(s)
- Melissa B. Oliver
- Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine University of Alabama at Birmingham, Birmingham, 35294 AL, USA;
- Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, 35294 AL, USA
| | - W. Edward Swords
- Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine University of Alabama at Birmingham, Birmingham, 35294 AL, USA;
- Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, 35294 AL, USA
- Correspondence:
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47
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Tsai MH, Liao SL, Chiu CY, Shih HJ, Hua MC, Yao TC, Lai SH, Yeh KW, Chen LC, Chang YJ, Huang JL. Longitudinal investigation of nasopharyngeal pneumococcal carriage in early childhood: The PATCH birth cohort study. PLoS One 2020; 15:e0237871. [PMID: 32817720 PMCID: PMC7446878 DOI: 10.1371/journal.pone.0237871] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 08/04/2020] [Indexed: 01/15/2023] Open
Abstract
Streptococcus pneumoniae is a common cause of infectious diseases such as pneumonia and sepsis. Its colonization is thought to be the first step in the development of invasive pneumococcal diseases. This study aimed to investigate pneumococcal colonization patterns in early childhood. A longitudinal birth cohort study was conducted for investigating nasopharyngeal colonized pneumococci at 1, 6, 12, 18, 24, and 36 months of age, particularly focusing on the serotype distribution and antimicrobial susceptibilities. Pneumococcal conjugate vaccine (PCV) effect on nasopharyngeal colonization was also assessed. During 2013-2017, 855 infants were enrolled and a total of 107 isolates were recovered from 95 infants during the first three years of life. In this period, the prevalence of pneumococcal colonization increased, with values ranging from 0.2% (2/834) at 1 month of age to 5.9% (19/323) at 36 months of age. The investigation of serotype revealed that 81.1% (73/90) belonged to the non-PCV13 serotypes-23A, 15A, 15C, and 15B. Moreover, PCV13 serotypes significantly decreased during 2014-2015, when routine PCV13 vaccination was initiated in Taiwan. PCV13 introduction may lead to the reduction in the rates of pneumococcal isolates resistant (R) to penicillin. Under conditional PCV13 vaccination, pneumococcal isolates primarily belonged to non-PCV13 serotypes. This non-PCV13 serotype replacement exhibited lower rates of penicillin R isolates, suggesting that PCV13 administration may reduce the antibiotic-nonsusceptible pneumococcal disease burden and antibiotic use.
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Affiliation(s)
- Ming-Han Tsai
- Department of Pediatrics, Chang Gung Memorial Hospital, Keelung, Taiwan
- Chang Gung University College of Medicine, Taoyuan, Taiwan
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- * E-mail: (JLH); (MHT)
| | - Sui-Ling Liao
- Department of Pediatrics, Chang Gung Memorial Hospital, Keelung, Taiwan
- Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chih-Yung Chiu
- Chang Gung University College of Medicine, Taoyuan, Taiwan
- Division of Pulmonology, Department of Pediatrics, Chang Gung Children’s Hospital, Taoyuan, Taiwan
| | - Hsiang-Ju Shih
- Department of Pediatrics, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Man-Chin Hua
- Department of Pediatrics, Chang Gung Memorial Hospital, Keelung, Taiwan
- Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsung-Chieh Yao
- Chang Gung University College of Medicine, Taoyuan, Taiwan
- Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Children’s Hospital, Taoyuan, Taiwan
| | - Shen-Hao Lai
- Chang Gung University College of Medicine, Taoyuan, Taiwan
- Division of Pulmonology, Department of Pediatrics, Chang Gung Children’s Hospital, Taoyuan, Taiwan
| | - Kuo-Wei Yeh
- Chang Gung University College of Medicine, Taoyuan, Taiwan
- Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Children’s Hospital, Taoyuan, Taiwan
| | - Li-Chen Chen
- Chang Gung University College of Medicine, Taoyuan, Taiwan
- Department of Pediatrics, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital and Chang Gung University, New Taipei, Taiwan
| | - Yi-Jung Chang
- Chang Gung University College of Medicine, Taoyuan, Taiwan
- Department of Pediatrics, Chang Gung Children’s Hospital, Taoyuan, Taiwan
| | - Jing-Long Huang
- Chang Gung University College of Medicine, Taoyuan, Taiwan
- Department of Pediatrics, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital and Chang Gung University, New Taipei, Taiwan
- * E-mail: (JLH); (MHT)
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48
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Lecrenier N, Marijam A, Olbrecht J, Soumahoro L, Nieto Guevara J, Mungall B. Ten years of experience with the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (Synflorix) in children. Expert Rev Vaccines 2020; 19:247-265. [DOI: 10.1080/14760584.2020.1738226] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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49
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Colijn C, Corander J, Croucher NJ. Designing ecologically optimized pneumococcal vaccines using population genomics. Nat Microbiol 2020; 5:473-485. [PMID: 32015499 PMCID: PMC7614922 DOI: 10.1038/s41564-019-0651-y] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Accepted: 12/03/2019] [Indexed: 12/14/2022]
Abstract
Streptococcus pneumoniae (the pneumococcus) is a common nasopharyngeal commensal that can cause invasive pneumococcal disease (IPD). Each component of current protein-polysaccharide conjugate vaccines (PCVs) generally induces immunity specific to one of the approximately 100 pneumococcal serotypes, and typically eliminates it from carriage and IPD through herd immunity. Overall carriage rates remain stable owing to replacement by non-PCV serotypes. Consequently, the net change in IPD incidence is determined by the relative invasiveness of the pre- and post-PCV-carried pneumococcal populations. In the present study, we identified PCVs expected to minimize the post-vaccine IPD burden by applying Bayesian optimization to an ecological model of serotype replacement that integrated epidemiological and genomic data. We compared optimal formulations for reducing infant-only or population-wide IPD, and identified potential benefits to including non-conserved pneumococcal carrier proteins. Vaccines were also devised to minimize IPD resistant to antibiotic treatment, despite the ecological model assuming that resistance levels in the carried population would be preserved. We found that expanding infant-administered PCV valency is likely to result in diminishing returns, and that complementary pairs of infant- and adult-administered vaccines could be a superior strategy. PCV performance was highly dependent on the circulating pneumococcal population, further highlighting the advantages of a diversity of anti-pneumococcal vaccination strategies.
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Affiliation(s)
- Caroline Colijn
- Department of Mathematics, Simon Fraser University, Burnaby, BC, Canada.
- Department of Mathematics, Imperial College London, London, UK.
| | - Jukka Corander
- Department of Biostatistics, University of Oslo, Oslo, Norway
- Helsinki Institute of Information Technology, Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland
- Parasites & Microbes, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
| | - Nicholas J Croucher
- MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK
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50
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Cockeran R, Dix-Peek T, Dickens C, Steel HC, Anderson R, Feldman C. Biofilm formation and induction of stress response genes is a common response of several serotypes of the pneumococcus to cigarette smoke condensate. J Infect 2020; 80:204-209. [DOI: 10.1016/j.jinf.2019.10.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 10/17/2019] [Accepted: 10/20/2019] [Indexed: 01/26/2023]
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