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  1. Arushothy R, Ahmad N
    Trop Biomed, 2008 Dec;25(3):259-61.
    PMID: 19287368
    Legionella pneumophila are intracellular pathogens, associated with human disease, attributed to the presence and absence of certain virulent genes. In this study, virulent gene loci (lvh and rtxA regions) associated with human disease were determined. Thirty-three cooling tower water isolates, isolated between 2004 to 2006, were analyzed for the presence of these genes by PCR method. Results showed that 19 of 33 (57.5%) of the L. pneumophila serogroup 1 isolates have both the genes. Six (18.2%) of the isolates have only the lvh gene and 2 (6.1%) of the isolates have only the rtxA gene. However, both genes were absent in 6 (18.2%) of the L. pneumophila isolates. The result of our study provides some insight into the presence of the disease causing L. pneumophila serogroup 1 in the environment. Molecular epidemiological studies will provide better understanding of the prevalence of the disease in Malaysia.
  2. Arushothy R, Amran F, Samsuddin N, Ahmad N, Nathan S
    PLoS Negl Trop Dis, 2020 12;14(12):e0008979.
    PMID: 33370273 DOI: 10.1371/journal.pntd.0008979
    BACKGROUND: Melioidosis is a neglected tropical disease with rising global public health and clinical importance. Melioidosis is endemic in Southeast Asia and Northern Australia and is of increasing concern in Malaysia. Despite a number of reported studies from Malaysia, these reports are limited to certain parts of the country and do not provide a cohesive link between epidemiology of melioidosis cases and the nation-wide distribution of the causative agent Burkholderia pseudomallei.

    METHODOLOGY/PRINCIPLE FINDINGS: Here we report on the distribution of B. pseudomallei sequence types (STs) in Malaysia and how the STs are related to STs globally. We obtained 84 culture-confirmed B. pseudomallei from confirmed septicaemic melioidosis patients from all over Malaysia. Prior to performing Multi Locus Sequence Typing, the isolates were subjected to antimicrobial susceptibility testing and detection of the YLF/BTFC genes and BimA allele. Up to 90.5% of the isolates were sensitive to all antimicrobials tested while resistance was observed for antimicrobials typically administered during the eradication stage of treatment. YLF gene cluster and bimABp allele variant were detected in all the isolates. The epidemiological distribution patterns of the Malaysian B. pseudomallei isolates were analysed in silico using phylogenetic tools and compared to Southeast Asian and world-wide isolates. Genotyping of the 84 Malaysian B. pseudomallei isolates revealed 29 different STs of which 6 (7.1%) were novel. ST50 was identified as the group founder followed by subgroup founders ST376, ST211 and ST84. A low-level diversity is noted for the B. pseudomallei isolates described in this study while phylogenetic analysis associated the Malaysian STs to Southeast Asian isolates especially isolates from Thailand. Further analysis also showed a strong association that implicates agriculture and domestication activities as high-risk routes of infection.

    CONCLUSIONS/SIGNIFICANCE: In conclusion, MLST analysis of B. pseudomallei clinical isolates from all states in Malaysia revealed low diversity and a close association to Southeast Asian isolates.

  3. 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.

  4. Arushothy R, Ahmad N, Amran F, Hashim R, Samsuddin N, Che Azih CR
    Genome Announc, 2018 Apr 19;6(16).
    PMID: 29674530 DOI: 10.1128/genomeA.00167-18
    After the introduction of the pneumococcal conjugate vaccine in Malaysia in recent years, the emergence of nonvaccine serotypes is of concern, particularly the antibiotic-resistant strains, with an increase specifically in serotype 15A. Here, we report the draft genome sequence of Streptococcus pneumoniae strain SS40_16, isolated from the blood sample of a 19-month-old female in 2016. SS40_16 is a multidrug-resistant strain with resistance to penicillin (MIC, ≥2 µg/ml), tetracycline, and trimethoprim-sulfamethoxazole. The strain belongs to serotype 15A and sequence type 1591 (ST1591).
  5. Arushothy R, Ramasamy H, Hashim R, Raj A S S, Amran F, Samsuddin N, et al.
    Int J Infect Dis, 2020 Jan;90:219-222.
    PMID: 31682962 DOI: 10.1016/j.ijid.2019.10.037
    The emergence of non-vaccine multidrug-resistant Streptococcus pneumoniae serotypes is on rise. This study was performed to investigate a highly resistant serotype 15A S. pneumoniae isolated from the blood specimen of a 20-month-old patient who died of her infection. The SS40_16 isolate was resistant to erythromycin, co-trimoxazole, tetracycline, and chloramphenicol, as well as to penicillin, ceftriaxone, and cefotaxime (using meningitis cut-off points, Clinical and Laboratory Standards Institute). The isolate belonged to sequence type 1591 (ST1591) and was related to CC81 clonal complex, suggesting the possibility of horizontal gene transfer. Scanning electron microscopy comparison between resistant and sensitive pneumococcal isolates also indicated similar phenotypic characteristics that confer high resistance. The emergence of highly resistant non-vaccine pneumococci is of great concern to public health and in the clinical setting. Pneumococcal surveillance programs represent a crucial tool, not only for determining the impact of pneumococcal conjugate vaccines, but also for monitoring the selective pressure of serotype replacement with regard to the treatment of invasive pneumococcal disease.
  6. Arushothy R, Mohd Ali MR, Zambri HF, Muthu V, Hashim R, Chieng S, et al.
    IJID Reg, 2024 Mar;10:94-99.
    PMID: 38179416 DOI: 10.1016/j.ijregi.2023.11.014
    OBJECTIVES: A leading cause of morbidity and mortality in Southeast Asia, the epidemiological data on melioidosis disease occurrence and mortality in Malaysia is not comprehensive. The aim of this study is to determine the burden of melioidosis and assess the National Surveillance for Antibiotic Resistance (NSAR) data as a potential tool melioidosis surveilance in Malaysia.

    METHODS: We performed a retrospective analysis on the B. pseudomallei reposited data submitted to the NSAR network between January 2014 and December 2020. The data were screened for information on patient demographics and specimen types. Additional patient comorbidities and outcomes were drawn from parallel surveillance for bacteremic melioidosis.

    RESULTS: The average annual incidence rate of melioidosis between 2014-2020 was 3.41 per 100,000 population and was significantly different between states (P <0.001). The highest incidence was observed in Pahang at 11.33 per 100,000 population. Individuals of Malay ethnicity, from the states of Pahang, Johor, Perak, and Negeri Sembilan aged 40-49, who were diabetic and working in agriculture-related sectors had a higher risk of succumbing to the infection.

    CONCLUSION: Assessing the NSAR data proved to be a useful tool for the determination of the incidence and socio-demographic risk factors attributed to melioidosis in Malaysia.

  7. 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.
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