Displaying publications 1 - 20 of 30 in total

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  1. Fulltext Serotype prevalence of Streptococcus pneumoniae in Malaysia - the need for carriage studies
    McNeil HC, Clarke SC
    Med J Malaysia, 2016 Jun;71(3):134-8.
    PMID: 27495888
    Pneumococcal disease, caused by the bacterium Streptococcus pneumoniae, is a major burden to global health. Although the World Health Organisation (WHO) strongly recommends the inclusion of pneumococcal conjugate vaccines in national immunisation programmes (NIP's) worldwide, this has not occurred in many countries in the WHO South East Asia and Western Pacific regions - particularly longstanding middle-income countries. It is widely accepted that carriage of S. pneumoniae is a precursor to developing any pneumococcal disease. The reduction in pneumococcal disease from vaccine serotypes (VT) following widespread implementation of the pneumococcal conjugate vaccine (PCV) is believed to be through the direct immunogenic protective effect of immunised individuals as well as indirectly through herd immunity diminishing the incidence of disease in nonimmunised individuals. In Malaysia, pneumococcal disease is not included in national surveillance programmes and although PCVs have been licensed, they have not been included in the NIP. Hence, the vaccine is only available privately and the majority of the population is not able to afford it. There is an urgent need to develop surveillance programmes in Malaysia to include pneumococcal serotype data from carriage and invasive disease so that it may help guide national vaccine policy prior to a decision being taken on the inclusion of PCVs in the NIP.
  2. 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.
  3. Challenges in mapping research investments for treatments against pneumonia
    Head MG, Fitchett JR, Clarke SC
    Lancet Infect Dis, 2015 Nov;15(11):1262.
    PMID: 26531036 DOI: 10.1016/S1473-3099(15)00351-5
  4. 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.
  5. 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.
  6. Phylogenetic relationship of non-typeable Haemophilus influenzae isolated in Malaysia
    Mohd-Zain Z, Kamsani NH, Ahmad N, Clarke SC
    Infect Genet Evol, 2015 Dec;36:240-3.
    PMID: 26394107 DOI: 10.1016/j.meegid.2015.09.017
    The epidemiology of non-typeable Haemophilus influenzae (NTHi) remains poorly understood. We therefore sought to determine the genetic relationship of 25 NTHi isolated from various states in Malaysia using multilocus sequence typing (MLST). The majority of isolates were obtained from sputum. There were 24 novel sequence types (STs). Eight isolates were single-locus variants, the remainder being singletons. Clustering was not based on clinical site of isolation or geographical origin. Despite the limited number of isolates examined in this study, we demonstrate that NTHi isolates in Malaysia are diverse and warrant further investigation.
  7. 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.
  8. Vaccine preventable meningitis in Malaysia: epidemiology and management
    McNeil HC, Jefferies JM, Clarke SC
    Expert Rev Anti Infect Ther, 2015 06;13(6):705-14.
    PMID: 25962101 DOI: 10.1586/14787210.2015.1033401
    Worldwide bacterial meningitis accounts for more than one million cases and 135,000 deaths annually. Profound, lasting neurological complications occur in 9-25% of cases. This review confirms the greatest risk from bacterial meningitis is in early life in Malaysia. Much of the disease burden can be avoided by immunization, particularly against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae. Despite inclusion of the Hib vaccine in the National Immunisation Programme and the licensure of pneumococcal vaccines, these two species are the main contributors to bacterial meningitis in Malaysia, with Neisseria meningitidis and Mycobacterium tuberculosis, causing a smaller proportion of disease. The high Hib prevalence may partly be due to dated, small-scale studies limiting the understanding of the current epidemiological situation. This highlights the need for larger, better quality surveillance from Malaysia to evaluate the success of Hib immunization and to help guide immunization policy for vaccines against S. pneumoniae and N. meningitidis.
  9. The state of ESKAPE in Malaysia
    McNeil HC, Lean SS, Lim V, Clarke SC
    Int J Antimicrob Agents, 2016 Nov;48(5):578-579.
    PMID: 27742200 DOI: 10.1016/j.ijantimicag.2016.08.011
  10. Lactoferrin modulates the biofilm formation and bap gene expression of methicillin-resistant Staphylococcus epidermidis
    Khanum R, Chung PY, Clarke SC, Chin BY
    Can J Microbiol, 2023 Feb 01;69(2):117-122.
    PMID: 36265186 DOI: 10.1139/cjm-2022-0135
    Lactoferrin is an innate glycoprotein with broad antibacterial and antibiofilm properties. The autonomous antibiofilm activity of lactoferrin against Gram-positive bacteria is postulated to involve the cell wall and biofilm components. Thus, the prevention of biomass formation and eradication of preformed biofilms by lactoferrin was investigated using a methicillin-resistant Staphylococcus epidermidis (MRSE) strain. Additionally, the ability of lactoferrin to modulate the expression of the biofilm-associated protein gene (bap) was studied. The bap gene regulates the production of biofilm-associated proteins responsible for bacterial adhesion and aggregation. In the in vitro biofilm assays, lactoferrin prevented biofilm formation and eradicated established biofilms for up to 24 and 72 h, respectively. Extensive eradication of MRSE biofilm biomass was accompanied by the significant upregulation of bap gene expression. These data suggest the interaction of lactoferrin with the biofilm components and cell wall of MRSE, including the biofilm-associated protein.
  11. The epidemiology of pneumococcal carriage and infections in Malaysia
    Le CF, Jefferies JM, Yusof MY, Sekaran SD, Clarke SC
    Expert Rev Anti Infect Ther, 2012 Jun;10(6):707-19.
    PMID: 22734960 DOI: 10.1586/eri.12.54
    In Malaysia, various aspects of the epidemiology of pneumococcal carriage and disease remain largely unclear due to the lack of supporting data. Although a number of relevant studies have been documented, their individual discrete findings are not sufficient to inform experts on pneumococcal epidemiology at a national level. Therefore, in this review we aim to bring together and systematically evaluate the key information regarding pneumococcal disease epidemiology in Malaysia and provide a comprehensive overview of the data. Major aspects discussed include pneumococcal carriage, disease incidence and prevalence, age factors, invasiveness of pneumococci, serotypes, molecular epidemiology and antibiotic susceptibility. Penicillin resistance is increasingly prevalent and studies suggest that the majority of pneumococcal serotypes causing pneumococcal disease in Malaysia are covered by currently available conjugate vaccines. Continued surveillance is needed to provide a better understanding of pneumococcal epidemiology in Malaysia.
  12. Fulltext Mapping pneumonia research: A systematic analysis of UK investments and published outputs 1997-2013
    Head MG, Fitchett JR, Newell ML, Scott JA, Harris JN, Clarke SC, et al.
    EBioMedicine, 2015 Sep;2(9):1193-9.
    PMID: 26501117 DOI: 10.1016/j.ebiom.2015.06.024
    BACKGROUND: The burden of pneumonia continues to be substantial, particularly among the poorest in global society. We describe here the trends for UK pneumonia R&D investment and published outputs, and correlate with 2013 global mortality.

    METHODS: Data related to awards to UK institutions for pneumonia research from 1997 to 2013 were systematically sourced and categorised by disease area and type of science. Investment was compared to mortality figures in 2010 and 2013 for pneumonia, tuberculosis and influenza. Investment was also compared to publication data.

    RESULTS: Of all infectious disease research between 2011 and 2013 (£917.0 million), £28.8 million (3.1%) was for pneumonia. This was an absolute and proportionate increase from previous time periods. Translational pneumonia research (33.3%) received increased funding compared with 1997-2010 where funding was almost entirely preclinical (87.5%, here 30.9%), but high-burden areas such as paediatrics, elderly care and antimicrobial resistance received little investment. Annual investment remains volatile; publication temporal trends show a consistent increase. When comparing investment to global burden with a novel 'investment by mortality observed' metric, tuberculosis (£48.36) and influenza (£484.21) receive relatively more funding than pneumonia (£43.08), despite investment for pneumonia greatly increasing in 2013 compared to 2010 (£7.39). Limitations include a lack of private sector data and the need for careful interpretation of the comparisons with burden, plus categorisation is subjective.

    CONCLUSIONS: There has been a welcome increase for pneumonia funding awarded to UK institutions in 2011-2013 compared with 1997-2010, along with increases for more translational research. Published outputs relating to pneumonia rose steadily from 1997 to 2013. Investment relative to mortality for pneumonia has increased, but it remains low compared to other respiratory infections and clear inequities remain. Analyses that measure investments in pneumonia can provide an insight into funding trends and research gaps.

    RESEARCH IN CONTEXT: Pneumonia continues to be a high-burden illness around the globe. This paper shows that although research funding is increasing in the UK (between 1997 and 2013), it remains poorly funded compared to other important respiratory infectious diseases such as tuberculosis and influenza. Publications about pneumonia have been steadily increasing over time, indicating continuing academic and clinical interest in the topic. Though global mortality of pneumonia is declining, it should still be an area of high priority for funders, policymakers and researchers.

  13. 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.

  14. Fulltext Informing pneumococcal conjugate vaccine policy in middle-income countries: The case of Malaysia
    Tricarico S, McNeil HC, Head MG, Cleary DW, Clarke SC, MYCarriage
    Vaccine, 2017 04 25;35(18):2288-2290.
    PMID: 28347503 DOI: 10.1016/j.vaccine.2017.03.053
  15. Fulltext Investment in pneumonia and pneumococcal research
    Head MG, Fitchett JR, Newell ML, Scott JAG, Clarke SC, Atun R
    Lancet Infect Dis, 2014 Nov;14(11):1037-1038.
    PMID: 25444398 DOI: 10.1016/S1473-3099(14)70949-1
  16. Fulltext Investigation of Upper Respiratory Carriage of Bacterial Pathogens among University Students in Kampar, Malaysia
    Ong HH, Toh WK, Thong LY, Phoon LQ, Clarke SC, Cheah ESG
    Trop Med Infect Dis, 2023 May 08;8(5).
    PMID: 37235317 DOI: 10.3390/tropicalmed8050269
    The carriage of bacterial pathogens in the human upper respiratory tract (URT) is associated with a risk of invasive respiratory tract infections, but the related epidemiological information on this at the population level is scarce in Malaysia. This study aimed to investigate the URT carriage of Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa among 100 university students by nasal and oropharyngeal swabbing. The presence of S. aureus, K. pneumoniae and P. aeruginosa was assessed via swab culture on selective media and PCR on the resulting isolates. For S. pneumoniae, H. influenzae and N. meningitidis, their presence was assessed via multiplex PCR on the total DNA extracts from chocolate agar cultures. The carriage prevalence of H. influenzae, S. aureus, S. pneumoniae, K. pneumoniae, N. meningitidis and P. aeruginosa among the subjects was 36%, 27%, 15%, 11%, 5% and 1%, respectively, by these approaches. Their carriage was significantly higher in males compared to females overall. The S. aureus, K. pneumoniae and P. aeruginosa isolates were also screened by the Kirby-Bauer assay, in which 51.6% of S. aureus were penicillin-resistant. The outcomes from carriage studies are expected to contribute to informing infectious disease control policies and guidelines.
  17. A brief history of and future prospects for pneumococcal vaccination in Malaysia
    Lister AJJ, Dombay E, Cleary DW, Sulaiman LH, Clarke SC
    Pneumonia (Nathan), 2023 Aug 25;15(1):12.
    PMID: 37620925 DOI: 10.1186/s41479-023-00114-8
    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.
  18. Genotypic characterization of Streptococcus pneumoniae serotype 19F in Malaysia
    Jeevajothi Nathan J, Mohd Desa MN, Thong KL, Clarke SC, Masri SN, Md Yasin R, et al.
    Infect Genet Evol, 2014 Jan;21:391-4.
    PMID: 24342879 DOI: 10.1016/j.meegid.2013.11.026
    Streptococcus pneumoniae is an epidemiologically important bacterial pathogen. Recently, we reported the antibiotic susceptibility patterns of a limited collection of pneumococcal isolates in Malaysia with a high prevalence of erythromycin resistant strains. In the present study, 55 of the pneumococcal isolates of serotype 19F were further analysed by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The generated genotypic patterns were then correlated with the antibiograms previously reported. Forty-seven different PFGE profiles (PTs) were obtained, showing that the isolates were genetically diverse. MLST identified 16 sequence types (STs) with ST-236 being predominant (58.2%), followed by ST-81 (10.3%). Among the ST-236 isolates, 22 were erythromycin resistant S. pneumoniae (ERSP) and 15 were trimethoprim/sulfamethoxazole (TMP/SMX) resistant, while among ST-81, four isolates were ERSP and two were TMP/SMX resistant. The high prevalence of erythromycin resistant serotype 19F isolates of ST-236 in this study has also been reported in other North and South East Asian countries.
  19. Prevalence and antimicrobial susceptibilities of Acinetobacter baumannii and non-baumannii Acinetobacters from Terengganu, Malaysia and their carriage of carbapenemase genes
    Mohd Rani F, A Rahman NI, Ismail S, Abdullah FH, Othman N, Alattraqchi AG, et al.
    J Med Microbiol, 2018 Nov;67(11):1538-1543.
    PMID: 30251951 DOI: 10.1099/jmm.0.000844
    A total of 153 non-repeat Acinetobacter spp. clinical isolates obtained in 2015 from Hospital Sultanah Nur Zahirah (HSNZ) in Terengganu, Malaysia, were characterized. Identification of the isolates at species level was performed by ribosomal DNA restriction analysis (ARDRA) followed by sequencing of the rpoB gene. The majority of the isolates (n=128; 83.7 %) were A. baumannii while the rest were identified as A. nosocomialis (n=16), A. calcoaceticus (n=5), A. soli (n=2), A. berezeniae (n=1) and A. variabilis (n=1). Multidrug resistance (MDR) was most prevalent in A. baumannnii (66.4 %) whereas only one non-baumannii isolate (A. nosocomialis) was MDR. The blaOXA-23 gene was the predominant acquired carbapenemase gene (56.2 %) and was significantly associated (P<0.001) with carbapenem resistance. However, no significant association was found for carbapenem resistance and isolates that contained the ISAba1-blaOXA-51 configuration.
  20. Fulltext Acinetobacter spp. infections in Malaysia: a review of antimicrobial resistance trends, mechanisms and epidemiology
    Mohd Rani F, A Rahman NI, Ismail S, Alattraqchi AG, Cleary DW, Clarke SC, et al.
    Front Microbiol, 2017;8:2479.
    PMID: 29312188 DOI: 10.3389/fmicb.2017.02479
    Acinetobacter spp. are important nosocomial pathogens, in particular the Acinetobacter baumannii-calcoaceticus complex, which have become a global public health threat due to increasing resistance to carbapenems and almost all other antimicrobial compounds. High rates of resistance have been reported among countries in Southeast Asia, including Malaysia. In this review, we examine the antimicrobial resistance profiles of Acinetobacter spp. hospital isolates from Malaysia over a period of nearly three decades (1987-2016) with data obtained from various peer-reviewed publications as well as the Malaysian National Surveillance on Antibiotic Resistance (NSAR). NSAR data indicated that for most antimicrobial compounds, including carbapenems, the peak resistance rates were reached around 2008-2009 and thereafter, rates have remained fairly constant (e.g., 50-60% for carbapenems). Individual reports from various hospitals in Peninsular Malaysia do not always reflect the nationwide resistance rates and often showed higher rates of resistance. We also reviewed the epidemiology and mechanisms of resistance that have been investigated in Malaysian Acinetobacter spp. isolates, particularly carbapenem resistance and found that blaOXA-23 is the most prevalent acquired carbapenemase-encoding gene. From the very few published reports and whole genome sequences that are available, most of the Acinetobacter spp. isolates from Malaysia belonged to the Global Clone 2 (GC2) CC92 group with ST195 being the predominant sequence type. The quality of data and analysis in the national surveillance reports could be improved and more molecular epidemiology and genomics studies need to be carried out for further in-depth understanding of Malaysian Acinetobacter spp. isolates.
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