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Fulltext The role of interspecies recombination in the evolution of antibiotic-resistant pneumococci

D'Aeth JC, van der Linden MP, McGee L, de Lencastre H, Turner P, Song JH, et al.

Elife, 2021 Jul 14;10.
PMID: 34259624 DOI: 10.7554/eLife.67113

Multidrug-resistant Streptococcus pneumoniae emerge through the modification of core genome loci by interspecies homologous recombinations, and acquisition of gene cassettes. Both occurred in the otherwise contrasting histories of the antibiotic-resistant S. pneumoniae lineages PMEN3 and PMEN9. A single PMEN3 clade spread globally, evading vaccine-induced immunity through frequent serotype switching, whereas locally circulating PMEN9 clades independently gained resistance. Both lineages repeatedly integrated Tn916-type and Tn1207.1-type elements, conferring tetracycline and macrolide resistance, respectively, through homologous recombination importing sequences originating in other species. A species-wide dataset found over 100 instances of such interspecific acquisitions of resistance cassettes and flanking homologous arms. Phylodynamic analysis of the most commonly sampled Tn1207.1-type insertion in PMEN9, originating from a commensal and disrupting a competence gene, suggested its expansion across Germany was driven by a high ratio of macrolide-to-β-lactam consumption. Hence, selection from antibiotic consumption was sufficient for these atypically large recombinations to overcome species boundaries across the pneumococcal chromosome.

Matched MeSH terms: Pneumococcal Vaccines
Economic Impact of Pneumococcal Protein-D Conjugate Vaccine (PHiD-CV) on the Malaysian National Immunization Programme

Aljunid S, Maimaiti N, Ahmed Z, Muhammad Nur A, Md Isa Z, Azmi S, et al.

Value Health Reg Issues, 2014 May;3:146-155.
PMID: 29702920 DOI: 10.1016/j.vhri.2014.04.008

OBJECTIVE: To assess the cost-effectiveness of introducing pneumococcal polysaccharide and nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in the National Immunization Programme of Malaysia. This study compared introducing PHiD-CV (10 valent vaccine) with current no vaccination, as well as against the alternative 13-valent pneumococcal conjugate vaccine (PCV13).

METHODS: A lifetime Markov cohort model was adapted using national estimates of disease burden, outcomes of pneumococcal disease, and treatment costs of disease manifestations including pneumonia, acute otitis media, septicemia, and meningitis for a hypothetical birth cohort of 550,000 infants. Clinical information was obtained by review of medical records from four public hospitals in Malaysia from the year 2008 to 2009. Inpatient cost from the four study hospitals was obtained from a diagnostic-related group-based costing system. Outpatient cost was estimated using clinical pathways developed by an expert panel. The perspective assessed was that of the Ministry of Health, Malaysia.

RESULTS: The estimated disease incidence was 1.2, 3.7, 70, and 6.9 per 100,000 population for meningitis, bacteremia, pneumonia, and acute otitis media, respectively. The Markov model predicted medical costs of Malaysian ringgit (RM) 4.86 billion (US $1.51 billion) in the absence of vaccination. Vaccination with PHiD-CV would be highly cost-effective against no vaccination at RM30,290 (US $7,407) per quality-adjusted life-year gained. On comparing PHiD-CV with PCV13, it was found that PHiD-CV dominates PCV13, with 179 quality-adjusted life-years gained while saving RM35 million (US $10.87 million).

CONCLUSIONS: It is cost-effective to incorporate pneumococcal vaccination in the National Immunization Programme of Malaysia. Our model suggests that PHiD-CV would be more cost saving than PCV13 from the perspective of the Ministry of Health of Malaysia.

Study site: UKM Medical Centre, Hospital Kuala Lumpur, Hospital
Alor Setar, and Hospital Queen Elizabeth, Kota Kinabalu

Matched MeSH terms: Pneumococcal Vaccines
The Health Economic Impact of Universal Infant Vaccination with the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine as Compared with 13-Valent Pneumococcal Conjugate Vaccine in Hong Kong

Lee KKC, Chia Wu DB, Topachevskyi O, Delgleize E, DeAntonio R

Value Health Reg Issues, 2013 May;2(1):64-74.
PMID: 29702855 DOI: 10.1016/j.vhri.2013.01.012

BACKGROUND: Pneumococcal universal vaccination in Hong Kong was introduced in 2009.
OBJECTIVES: We assessed the health and economic impact of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PCV-10) compared with the current 13-valent pneumococcal conjugate vaccine (PCV-13) recommended for Hong Kong in 2011, providing new elements to be considered by public health authorities in the future decision-making process for pneumococcal vaccines in this country.
METHODS: An analytical model was used to estimate the annual economic and health outcomes of invasive pneumococcal disease (IPD), community-acquired pneumonia, and acute otitis media (AOM), including nontypeable H. influenzae-related AOM, for a birth cohort in Hong Kong from the payer perspective with a 10-year horizon. Clinical impact including morbidity-mortality, quality-adjusted life-years (QALYs), incremental costs, and cost-effectiveness comparing PCV-10 and PCV-13 were estimated. Probabilistic sensitivity analyses by using alternate scenarios were performed.
RESULTS: Model projections indicate that PCV-13 and PCV-10 have approximately equivalent impact on the prevention of deaths caused by IPD and pneumonia. PCV-13 is projected to prevent 6 additional cases of IPD, whereas PCV-10 is projected to prevent 13,229 additional AOM cases and 101 additional QALYs. For the base case, PCV-10 vaccination is estimated to save 44.6 million Hong Kong dollars (34.1 million Hong Kong dollars discounted). Sensitivity analysis indicated that PCV-10 would generate more QALYs and save costs as compared with PCV-13.
CONCLUSIONS: Universal infant vaccination with new available pneumococcal vaccines is expected to generate a significant additional impact on reducing the burden of pneumococcal diseases in Hong Kong. PCV-10 vaccination would be potentially a cost-saving strategy compared with PCV-13 vaccination, generating better cost offsets and higher QALY gains.

Matched MeSH terms: Pneumococcal Vaccines
Choosing between 7-, 10- and 13-valent pneumococcal conjugate vaccines in childhood: a review of economic evaluations (2006-2014)

Wu DB, Chaiyakunapruk N, Chong HY, Beutels P

Vaccine, 2015 Mar 30;33(14):1633-58.
PMID: 25681663 DOI: 10.1016/j.vaccine.2015.01.081

BACKGROUND: Seven-valent pneumococcal conjugate vaccines (PCV7) have been used in children for more than a decade. Given the observed increase in disease caused by pneumococcal serotypes not covered by PCV7, an increasing number of countries are switching from 7-valent to 10- and 13-valent PCVs ("PCV10" and "PCV13"). Economic evaluations are important tools to inform decisions and price negotiations to make such a switch.
OBJECTIVE: This review aims to provide a critical assessment of economic evaluations involving PCV10 or PCV13, published since 2006.
METHODS: We searched Scopus, ISI Web of Science (SCI and SSCI) and Pubmed to retrieve, select and review relevant studies, which were archived between 1st January 2006 and 31st January 2014. The review protocol involved standard extraction of assumptions, methods, results and sponsorships from the original studies.
RESULTS: Sixty-three economic evaluations on PCVs published since January 2006 were identified. About half of these evaluated PCV10 and/or PCV13, the subject of this review. At current prices, both PCV13 and PCV10 were likely judged preferable to PCV7. However, the combined uncertainty related to price differences, burden of disease, vaccine effectiveness, herd and serotype replacement effects determine the preference base for either PCV10 or PCV13. The pivotal assumptions and results of these analyses also depended on which manufacturer sponsored the study.
CONCLUSION: A more thorough exploration of uncertainty should be made in future analyses on this subject, as we lack understanding to adequately model herd and serotype replacement effects to reliably predict the population impact of PCVs. The introduction of further improved PCVs in an environment of evolving antibiotic resistance and under the continuing influence of previous PCVs implies that the complexity and data requirements for relevant analyses will further increase. Decision makers using these analyses should not just rely on an analysis from a single manufacturer.
KEYWORDS: Cost-effectiveness; Cost–benefit; Pneumococcal conjugate vaccine; Streptococcus pneumoniae

Matched MeSH terms: Pneumococcal Vaccines/economics*
Vaccination in Southeast Asia--reducing meningitis, sepsis and pneumonia with new and existing vaccines

Richardson A, Morris DE, Clarke SC

Vaccine, 2014 Jul 16;32(33):4119-23.
PMID: 24907487 DOI: 10.1016/j.vaccine.2014.05.062

Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis are leading causes of vaccine-preventable diseases such as meningitis, sepsis and pneumonia. Although there has been much progress in the introduction of vaccines against these pathogens, access to vaccines remains elusive in some countries. This review highlights the current S. pneumoniae, H. influenzae type b, and N. meningitidis immunization schedules in the 10 countries belonging to the Association of Southeast Asian Nations (ASEAN). Epidemiologic studies may be useful for informing vaccine policy in these countries, particularly when determining the cost-effectiveness of introducing new vaccines.

Matched MeSH terms: Pneumococcal Vaccines*
Prevalence of Streptococcus pneumoniae serotypes causing invasive and non-invasive disease in South East Asia: a review

Jauneikaite E, Jefferies JM, Hibberd ML, Clarke SC

Vaccine, 2012 May 21;30(24):3503-14.
PMID: 22475858 DOI: 10.1016/j.vaccine.2012.03.066

BACKGROUND: Streptococcus pneumoniae is a major cause of bacterial infections resulting in significant morbidity and mortality worldwide. Currently, up to 13 serotypes are included in pneumococcal conjugate vaccines (PCVs). However, the serotype formulation of these vaccines was initially designed to protect children against serotypes most commonly causing invasive disease in North America, and may not reflect the serotype distribution across the world. Data regarding pneumococcal epidemiology from the other parts of the world, in particular South East Asia, has not been reviewed.
METHODS: This systematic literature review analyses published serotype data regarding S. pneumoniae isolates from South East Asian countries (defined as countries belonging to the Association of South East Asian Nations, ASEAN): Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand and Vietnam up to 3rd of March 2012.
RESULTS: Analysis of data from six ASEAN countries, from which information on pneumococcal serotypes was available, showed that the most common disease causing serotypes (in rank order) were 19F, 23F, 14, 6B, 1, 19A and 3. Serotype distribution of pneumococcal isolates was similar across the ASEAN region. Serotype level data was more commonly reported for pneumococcal isolates causing invasive pneumococcal disease than for those from non-invasive disease. Studies from Malaysia, Thailand and Singapore contributed the largest proportion of pneumococcal isolates, and serotype data, when compared to other ASEAN countries.
CONCLUSION: This review demonstrates that the majority of IPD causing serotypes in SE Asia are included in currently licensed PCVs. However, PCV's are included in the routine childhood immunisation schedule of only one of the ten countries included in this analysis. Our findings demonstrate the scarcity of information available on serotype prevalence and distribution of pneumococci in SE Asia.

Matched MeSH terms: Pneumococcal Vaccines/administration & dosage; Pneumococcal Vaccines/immunology
Changes in serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates from adult patients in Asia: Emergence of drug-resistant non-vaccine serotypes

Kim SH, Chung DR, Song JH, Baek JY, Thamlikitkul V, Wang H, et al.

Vaccine, 2020 08 27;38(38):6065-6073.
PMID: 31590932 DOI: 10.1016/j.vaccine.2019.09.065

This study was performed to investigate the serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae in Asian countries. A prospective surveillance study on S. pneumoniae collected from adult patients (≥50 years old) with invasive pneumococcal disease or community-acquired pneumonia was performed at 66 hospitals in Asian countries (Korea, China, Malaysia, Singapore, the Philippines, and Thailand) in 2012-2017. Serotyping and antimicrobial susceptibility tests of 850 pneumococcal isolates were performed. The proportions of isolates with serotypes covered by 13-valent pneumococcal conjugate vaccine (PCV13) were 37.0% in Korea, 53.4% in China, 77.2% in Malaysia, 35.9% in the Philippines, 68.7% in Singapore, and 60.2% in Thailand. Major serotypes were 19F (10.4%), 19A (10.1%), and 3 (8.5%) in 2012-2017, with different serotype distributions in each country. Macrolide resistance in pneumococci was high (66.8%) and prevalence of multidrug resistance (MDR) also remained high (50.8%). MDR non-PCV13 serotypes such as 11A, 15A, 35B, and 23A have emerged in Asian countries. This study showed the persistent prevalence of 19F and 19A with a noteworthy increase of certain non-PCV13 serotypes in Asian countries. High prevalence of macrolide resistance and MDR was also found in pneumococcal isolates. These data emphasize the need for continued surveillance of pneumococcal epidemiology in Asia in the post-pneumococcal vaccine era.

Matched MeSH terms: Pneumococcal Vaccines
Vaccine-induced immune thrombocytopaenia purpura in autologous haematopoietic stem cell transplantation

Wan Jamaludin WF, Kok WH, Loong L, Palaniappan SK, Zakaria MZ, Ong TC, et al.

Med J Malaysia, 2018 12;73(6):430-432.
PMID: 30647224

Immune Thrombocytopenia Purpura (ITP) secondary to vaccinations is rare, especially after autologous hematopoietic stem cell transplantation (HSCT). A 31-yearold female received autologous HSCT for relapsed Hodgkin Disease, with platelet engraftment at Day+14. One week after receiving second scheduled vaccinations, she developed severe thrombocytopenia (3x109/L) associated with pharyngeal hematoma. Bone marrow (BM) examinations were consistent with ITP, possibly secondary to Influenza vaccine. Platelet increment was poor despite high dose corticosteroids, intravenous immunoglobulin (IVIG), Danazol and Eltrombopag. A repeated BM biopsy was in agreement with ITP. Re-treatment with tapering doses of prednisolone resulted in stable platelet counts at 120x109/L a year later.

Matched MeSH terms: Pneumococcal Vaccines/adverse effects
Fulltext Predominance of ST320 among Streptococcus pneumoniae serotype 19A isolates from 10 Asian countries

Shin J, Baek JY, Kim SH, Song JH, Ko KS

J Antimicrob Chemother, 2011 May;66(5):1001-4.
PMID: 21393143 DOI: 10.1093/jac/dkr048

BACKGROUND: After 7-valent pneumococcal conjugate vaccine (PCV7) introduction, non-vaccine serotypes such as 19A are increasing among Streptococcus pneumoniae. However, only limited data on 19A S. pneumoniae are available in Asian countries.
METHODS: Out of 1637 S. pneumoniae clinical pneumonia isolates collected during 2008 and 2009 from 10 Asian countries (Korea, Malaysia, Taiwan, Thailand, Saudi Arabia, Hong Kong, India, Japan, the Philippines and Vietnam), 91 serotype 19A S. pneumoniae isolates were identified. Capsular swelling reaction identified serotype 19A isolates. Antimicrobial susceptibility testing was performed on the serotype 19A isolates using the broth microdilution method, and the genotypes of the isolates were assessed using multilocus sequence typing.
RESULTS: Thirty different sequence types (STs) were identified. The most prevalent clone was ST320 (46 isolates, 51.1%). ST320 was found in Hong Kong, India, Korea, Malaysia, Saudi Arabia and Taiwan. ST320 isolates were mostly multidrug resistant (MDR) and showed significantly higher resistance rates than other STs for cefuroxime, clindamycin, and trimethoprim/sulfamethoxazole.
CONCLUSIONS: Although diverse clones were identified among 19A S. pneumoniae isolates, MDR ST320 was the predominant clone in Asian countries. Its predominance, even in countries with no or low coverage of PCV7, may indicate that its emergence and dissemination was due to more than just vaccine selection pressure in Asian countries. A longitudinal investigation of the change of serotypes and genotypes since the introduction of PCV7 is required to understand the emergence and dissemination mechanisms of a certain clone of 19A S. pneumoniae isolates.

Matched MeSH terms: Pneumococcal Vaccines/administration & dosage; Pneumococcal Vaccines/immunology
Fulltext Serotype distribution of invasive, non-invasive and carried Streptococcus pneumoniae in Malaysia: a meta-analysis

Lister AJJ, Le CF, Cheah ESG, Desa MNM, Cleary DW, Clarke SC

Pneumonia (Nathan), 2021 May 25;13(1):9.
PMID: 34030731 DOI: 10.1186/s41479-021-00086-7

BACKGROUND: Pneumococcal pneumonia is the leading cause of under-five mortality globally. The surveillance of pneumococcal serotypes is therefore vital for informing pneumococcal vaccination policy and programmes. Pneumococcal conjugate vaccines (PCVs) have been available as an option in the private healthcare setting and beginning December 2020, PCV10 was incorporated as part of routine national immunisation programme (NIP) in Malaysia. We searched existing literature on pneumococcal serotype distribution across Malaysia to provide an overall view of this distribution before the implementation of PCV10.
METHODS: Online databases (PubMed, Ovid MEDLINE and Scopus), reference lists of articles identified, and grey literature (Malaysian Ministry of Health website, WHO website) were systematically searched for relevant literature on pneumococcal serotype distribution across Malaysia up to 10th November 2020. No lower date limit was set to maximise the number of target reports returned. Results of serotypes were split by age categories, including ≤5 years, > 5 years and unreported for those that did not specify.
RESULTS: The search returned 18 relevant results, with a total of 2040 isolates. The most common serotypes across all disease types were 19F (n = 313, 15.3% [95%CI: 13.8-17.0]), 23F (n = 166, 8.1% [95%CI: 7.0-9.4]), 14 (n = 166, 8.1% [95%CI: 7.0-9.4]), 6B (n = 163, 8.0% [95%CI: 6.9-9.2]) and 19A (n = 138, 6.8% [95%CI: 5.8-7.9]).
CONCLUSION: Four of the most common serotypes across all isolate sources in Malaysia are covered by PCV10, while PCV13 provides greater serotype coverage in comparison to PCV10. There is still a need for surveillance studies, particularly those investigating serotypes in children under 5 years of age, to monitor vaccine effectiveness and pneumococcal population dynamic following implementation of PCV10 into routine immunisation.

Matched MeSH terms: Pneumococcal Vaccines
Fulltext Novel clones of Streptococcus pneumoniae causing invasive disease in Malaysia

Jefferies JM, Mohd Yusof MY, Devi Sekaran S, Clarke SC

PLoS One, 2014;9(6):e97912.
PMID: 24941079 DOI: 10.1371/journal.pone.0097912

Although Streptococcus pneumoniae is a leading cause of childhood disease in South East Asia, little has previously been reported regarding the epidemiology of invasive pneumococcal disease in Malaysia and very few studies have explored pneumococcal epidemiology using multilocus sequence typing (MLST). Here we describe serotype, multilocus sequence type (ST), and penicillin susceptibility of thirty pneumococcal invasive disease isolates received by the University of Malaya Medical Centre between February 2000 and January 2007 and relate this to the serotypes included in current pneumococcal conjugate vaccines. A high level of diversity was observed; fourteen serotypes and 26 sequence types (ST), (11 of which were not previously described) were detected from 30 isolates. Penicillin non-susceptible pneumococci accounted for 33% of isolates. The extent of molecular heterogeneity within carried and disease-causing Malaysian pneumococci remains unknown. Larger surveillance and epidemiological studies are now required in this region to provide robust evidence on which to base future vaccine policy.

Matched MeSH terms: Pneumococcal Vaccines/administration & dosage*; Pneumococcal Vaccines/chemistry
Fulltext Capsular serotype and antibiotic resistance of Streptococcus pneumoniae isolates in Malaysia

Le CF, Palanisamy NK, Mohd Yusof MY, Sekaran SD

PLoS One, 2011;6(5):e19547.
PMID: 21603602 DOI: 10.1371/journal.pone.0019547

BACKGROUND: Streptococcus pneumoniae is a major causative agent of severe infections, including sepsis, pneumonia, meningitis, and otitis media, that has since become a major public health concern. In this study, the serotypes distribution of pneumococcal isolates was investigated to predict the efficacy of the 7-valent pneumococcal conjugate vaccine (PCV7) among the Malaysian populations.
METHODOLOGY/PRINCIPAL FINDINGS: A total of 151 clinical isolates were serotyped using multiplex PCR assays. Out of them, there were 21.2% penicillin-resistant, 29.1% penicillin-intermediate, and 49.7% penicillin-susceptible S. pneumoniae strains. Serotypes detected among the Malaysian isolates were 1, 3, 10A, 11A/11D, 12F/12A, 14, 15A, 15B/15C, 16F, 18C/18B/18A/18F, 19A, 19F, 23F, 35B, 35F/47F, 6A/6B, 7C/7B/40, 7F/7A, 9V/9A, and 34. Serotype 19F and 23F were the two most prevalent serotypes detected. Serotypes are highly associated with invasiveness of isolates (p = 0.001) and penicillin susceptibility (p<0.001). Serotype 19F was observed to have increased resistance against penicillin while serotype 19A has high invasive tendency. Age of patients was an important factor underlying the pneumococcal serotypes (p = 0.03) and clinical sites of infections (p<0.001). High prevalence of pneumococcal isolates were detected among children <5 years old at nasopharyngeal sites while elderly adults ≥60 years old were at increased risk for pneumococcal bacteremia.
CONCLUSION/SIGNIFICANCE: Current study revealed that a number of serotypes, especially those associated with high penicillin resistance, have been formulated in the PCV7. Therefore, the protections expected from the routine use of PCV7 would be encouraging for the Malaysian. However, it is not possible to predict serotypes that might become predominant in the future and hence continued surveillance of circulating serotypes will be needed.

Matched MeSH terms: Pneumococcal Vaccines/immunology*
Cost Effectiveness of Pneumococcal Vaccination in Children in Low- and Middle-Income Countries: A Systematic Review

Saokaew S, Rayanakorn A, Wu DB, Chaiyakunapruk N

Pharmacoeconomics, 2016 12;34(12):1211-1225.
PMID: 27510721

BACKGROUND: Although pneumococcal conjugate vaccines (PCVs) have been available for prevention of invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae (S. pneumoniae) for over a decade, their adoption into national immunization programmes in low- and middle-income countries (LMICs) is still limited. Economic evaluations (EEs) play a crucial role in support of evidence-informed decisions.
OBJECTIVE: This systematic review aims to provide a critical summary of EEs of PCVs and identify key drivers of EE findings in LMICs.
METHODS: We searched Scopus, ISI Web of Science, PubMed, Embase and Cochrane Central from their inception to 30 September 2015 and limited the search to LMICs. The search was undertaken using the search strings 'pneumococc* AND conjugat* AND (vaccin* OR immun*)' AND 'economic OR cost-effectiveness OR cost-benefit OR cost-utility OR cost-effectiveness OR cost-benefit OR cost-utility' in the abstract, title or keyword fields. To be included, each study had to be a full EE of a PCV and conducted for an LMIC. Studies were extracted and reviewed by two authors. The review involved standard extraction of the study overview or the characteristics of the study, key drivers or parameters of the EE, assumptions behind the analyses and major areas of uncertainty.
RESULTS: Out of 134 records identified, 22 articles were included. Seven studies used a Markov model for analysis, while 15 studies used a decision-tree analytic model. Eighteen studies performed a cost-utility analysis (CUA), with disability-adjusted life-years, quality-adjusted life-years or life-years gained as a measure of health outcome, while four studies focused only on cost-effectiveness analysis (CEA). Both CEA and CUA findings were provided by eight studies. Herd effects and serotype replacement were considered in 10 and 13 studies, respectively. The current evidence shows that both the 10-valent and 13-valent PCVs are probably cost effective in comparison with the 7-valent PCV or no vaccination. The most influential parameters were vaccine efficacy and coverage (in 16 of 22 studies), vaccine price (in 13 of 22 studies), disease incidence (in 11 of 22 studies), mortality from IPD and pneumonia (in 8 of 22 studies) and herd effects (in 4 of 22 studies). The findings were found to be supportive of the products owned by the manufacturers.
CONCLUSION: Our review demonstrated that an infant PCV programme was a cost-effective intervention in most LMICs (in 20 of 22 studies included). The results were sensitive to vaccine efficacy, price, burden of disease and sponsorship. Decision makers should consider EE findings and affordability before adoption of PCVs.

Matched MeSH terms: Pneumococcal Vaccines/administration & dosage*; Pneumococcal Vaccines/economics
Immune response to influenza vaccine and pneumococcal polysaccharide vaccine under IL-6 signal inhibition therapy with tocilizumab

Tsuru T, Terao K, Murakami M, Matsutani T, Suzaki M, Amamoto T, et al.

Mod Rheumatol, 2014 May;24(3):511-6.
PMID: 24252023 DOI: 10.3109/14397595.2013.843743

To evaluate humoral immune response to influenza vaccine and polysaccharide pneumococcal vaccine in patients with rheumatoid arthritis (RA) or Castleman's disease (CD) during tocilizumab therapy.

Matched MeSH terms: Pneumococcal Vaccines/immunology*
Fulltext Incidence of pneumococcal meningitis in children less than 5 years age in Malaysia, Singapore and Thailand: a review

Maimaiti, Namaitijiang, Lotfizadeh, Masoud, Zafar Ahmed, Azam Rahimi, Jadoo, Saad Ali, Aljunid, Syed

Malaysian Journal of Public Health Medicine, 2015;15(1):0-0.
MyJurnal

Streptococcus pneumoniae (pneumococcus) is the most common cause of community-acquired pneumonia, meningitis, and bacteremia in children and adults, including the elderly, and is responsible for high rates of morbidity and mortality worldwide. Aim of this paper to review published articles on incidence of pneumococcal meningitis in children less than 5 years of age in Malaysia, Singapore and Thailand, and compare the incidence of pneumococcal meningitis among the children in the three courtiers. Literature searches were conducted using google scholar, PubMed, the World Health Organization (WHO) website of the Weekly Epidemiological Record, and the countries’ Ministry of Health (MOH) website, and were limited to articles written in English. All relevant publications/abstracts published/presented during the period December 2000 through March 2014. Searches were conducted from April 1, 2014, till July 11, 2014 using various combinations of the following search terms “ Pneumococcal diseases” OR “meningococcal” OR “pneumococcal meningitis” OR “meningococcus”. A total of five articles and abstracts described the incidence of pneumococcal meningitis among children 5 years old. These five documents include two conference abstracts from Malaysia, one published paper from Singapore and two published papers from Thailand. The Malaysian, Singaporean and Thai pneumococcal meningitis incidence rate was 3.8-8.6, 2.3 and 0.10-1.8 per 100,000 children respectively. Our review confirmed that the incidence rate of pneumococcal meningitis was vary among the countries. The highest incidence rate of pneumococcal meningitis was found in Malaysia followed by Singapore and Thailand.

Matched MeSH terms: Pneumococcal Vaccines
Fulltext Invasive pneumococcal disease in a tertiary paediatric hospital in Malaysia

Aisha Fadhilah Abang Abdullah, Kee, Sze Ying, Kamarul Azhar Mohd Razali, Jamal Mohamed, Thahira A., Zubaidah Abdul Wahab, Norlijah Othman

Malaysian Journal of Paediatrics and Child Health, 2017;23(1):0-0.
MyJurnal

Introduction and Objective: Pneumococcal disease is a leading cause of morbidity and mortality worldwide. There were limited publications on invasive pneumococcal infection (IPD) in Malaysia. The aim of this study is to describe restrospectively cases of IPD in hospitalised children of less than 12 years old and highlighting the unusual cases.

Methodology: A retrospective review of children with IPD from March 2002 to November 2005 at a tertiary paediatric hospital. IPD cases were defined as isolates of Streptococcus pneumoniae from a normally sterile body fluid site.

Results: Twenty-four patients were identified with a male preponderance. Two-thirds of patients were below 1-year-old; with three cases presenting in the premature newborn. Thirty-seven percent of cases had underlying conditions. Sepsis and pneumonia were the commonest manifestation, followed by meningitis. The unusual manifestations were in a form of postinfectious glomerulonephritis and overwhelming purpura fulminans. There were two mortalities; both infants had meningitis. Antibiotic susceptibility pattern showed that more than half of the isolates were sensitive towards penicillin and erythromycin. Penicillin resistance was found in 6 (25%) isolates. Conclusion: IPD results in significant morbidity and mortality, especially in young children below 2 years of age and justifies further evaluation of preventive strategies including the implementation of pneumococcal vaccine in the national immunisation programme.

Matched MeSH terms: Pneumococcal Vaccines
Fulltext Nasopharyngeal Bacterial Carriage in the Conjugate Vaccine Era with a Focus on Pneumococci

Devine VT, Jefferies JM, Clarke SC, Faust SN

J Immunol Res, 2015;2015:394368.
PMID: 26351646 DOI: 10.1155/2015/394368

Seven-valent pneumococcal conjugate vaccine (PCV7) was included in the UK national immunisation program in 2006, and this was replaced by thirteen-valent PCV in 2010. During this time, the carriage of vaccine-type Streptococcus pneumoniae decreased but pneumococcal carriage remained stable due to increases in non-vaccine-type S. pneumoniae. Carriage studies have been undertaken in various countries to monitor vaccine-type replacement and to help predict the serotypes, which may cause invasive disease. There has been less focus on how conjugate vaccines indirectly affect colonization of other nasopharyngeal bacteria. If the nasopharynx is treated as a niche, then bacterial dynamics are accepted to occur. Alterations in these dynamics have been shown due to seasonal changes, antibiotic use, and sibling/day care interaction. It has been shown that, following PCV7 introduction, an eradication of pneumococcal vaccine types has resulted in increases in the abundance of other respiratory pathogens including Haemophilus influenzae and Staphylococcus aureus. These changes are difficult to attribute to PCV7 introduction alone and these studies do not account for further changes due to PCV13 implementation. This review aims to describe nasopharyngeal cocarriage of respiratory pathogens in the PCV era.

Matched MeSH terms: Pneumococcal Vaccines/immunology*
Pilus islets and the clonal spread of piliated Streptococcus pneumoniae: A review

Dzaraly ND, Muthanna A, Mohd Desa MN, Taib NM, Masri SN, Rahman NIA, et al.

Int J Med Microbiol, 2020 Oct;310(7):151449.
PMID: 33092697 DOI: 10.1016/j.ijmm.2020.151449

Pneumococci are a common cause of severe infections, such as otitis media, pneumonia, meningitis and bacteremia. Pili are detected in a small proportion of pneumococcal population, but these structures have recently been associated with bacterial virulence in humans. Therefore, the epidemiological relationships between pneumococcal pili, serotype and antimicrobial resistance are of interest. This study aims to discuss the virulence contribution of the Streptococcus pneumoniae pili and the epidemiological relationships among the pilus genes, antimicrobial resistance trends, regional serotypes and genotypic variations. Previous reports have characterized the pneumococcal pilus islet as a clonal feature in the pneumococcal serotypes that are covered by the pneumococcal conjugate vaccine (PCV), including serotypes 19A, 19F, 23F and 7F. Many of the pneumococcal molecular epidemiology network (PMEN) clones are piliated isolates that are also strongly associated with a high frequency of multidrug resistance. Most of these piliated pneumococcal isolates belong to a few clonal complexes (CC), such as CC320, CC199, CC271, CC191 and CC156. Additional molecular epidemiology and genomic studies, particularly whole genome sequence analysis (WGS), are needed to develop an in-depth understanding of the piliated pneumococcal isolates.

Matched MeSH terms: Pneumococcal Vaccines
Fulltext Pneumococcal serotype distribution and antibiotic susceptibility in Malaysia: A four-year study (2014-2017) on invasive paediatric isolates

Arushothy R, Ahmad N, Amran F, Hashim R, Samsudin N, Azih CRC

Int J Infect Dis, 2019 Mar;80:129-133.
PMID: 30572022 DOI: 10.1016/j.ijid.2018.12.009

OBJECTIVE: This study was performed to analyze the serotype distribution of Streptococcus pneumoniae causing invasive pneumococcal disease (IPD) in children aged 5 years and under in Malaysia and to assess the antimicrobial resistance.
METHODS: From 2014 to 2017, a total of 245 invasive S. pneumoniae isolates from children ≤5 years of age were received from hospitals all around Malaysia. All isolates were identified and subjected to serotyping and antimicrobial susceptibility testing.
RESULTS: Of the 245 isolates, 117 (48.0%) were from children aged <1year, 46 (19.05%) were from children aged 1-2 years, and 82 (33.0%) were from children aged 2-5 years. The most common serotypes were 14 (26.9%), 6B (19.6%), 19A (11.8%), 6A (10.6%), and 19F (6.9%) and vaccine coverage was 88.2% for PCV13, 64.1% for PCV10, and 63.3% for PCV7. Resistance to penicillin was 0.2% for non-meningitis cases and 22.2% for meningitis cases; erythromycin resistance was reported in 42.9%, co-trimoxazole in 35.9%, and tetracycline in 42.9%.
CONCLUSIONS: Serotypes 14, 6B, 19A, 6A, and 19F were the most common serotypes isolated from children with IPD in Malaysia during this pre-vaccination era. The lack of reports on the serotype distribution has limited action for the implementation of PCV in the national immunization programme (NIP). The information from this study may benefit future policies for the introduction of PCV in the Malaysian NIP and ultimately may reduce the morbidity and mortality among children in Malaysia.

Matched MeSH terms: Pneumococcal Vaccines
Fulltext Cost-effectiveness analysis of infant universal routine pneumococcal vaccination in Malaysia and Hong Kong

Wu DB, Roberts C, Lee VW, Hong LW, Tan KK, Mak V, et al.

Hum Vaccin Immunother, 2016;12(2):403-16.
PMID: 26451658 DOI: 10.1080/21645515.2015.1067351

Pneumococcal disease causes large morbidity, mortality and health care utilization and medical and non-medical costs, which can all be reduced by effective infant universal routine immunization programs with pneumococcal conjugate vaccines (PCV). We evaluated the clinical and economic benefits of such programs with either 10- or 13-valent PCVs in Malaysia and Hong Kong by using an age-stratified Markov cohort model with many country-specific inputs. The incremental cost per quality-adjusted life year (QALY) was calculated to compare PCV10 or PCV13 against no vaccination and PCV13 against PCV10 over a 10-year birth cohort's vaccination. Both payer and societal perspectives were used. PCV13 had better public health and economic outcomes than a PCV10 program across all scenarios considered. For example, in the base case scenario in Malaysia, PCV13 would reduce more cases of IPD (+2,296), pneumonia (+705,281), and acute otitis media (+376,967) and save more lives (+6,122) than PCV10. Similarly, in Hong Kong, PCV13 would reduce more cases of IPD cases (+529), pneumonia (+172,185), and acute otitis media (+37,727) and save more lives (+2,688) than PCV10. During the same time horizon, PCV13 would gain over 74,000 and 21,600 additional QALYs than PCV10 in Malaysia and Hong Kong, respectively. PCV13 would be cost saving when compared against similar program with PCV10, under both payer and societal perspective in both countries. PCV13 remained a better choice over PCV10 in multiple sensitivity, scenario, and probabilistic analyses. PCV13s broader serotype coverage in its formulation and herd effect compared against PCV10 were important drivers of differences in outcomes.

Matched MeSH terms: Pneumococcal Vaccines/immunology

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