Displaying publications 61 - 80 of 99 in total

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  1. Ab-Rahman HA, Wong PF, Rahim H, Abd-Jamil J, Tan KK, Sulaiman S, et al.
    Springerplus, 2015;4:665.
    PMID: 26558168 DOI: 10.1186/s40064-015-1463-z
    INTRODUCTION: HPS is a potentially life-threatening histiocytic disorder that has been described in various viral infections including dengue. Its involvement in severe and fatal dengue is probably more common but is presently under recognized.
    CASE DESCRIPTION: A 38-year-old female was admitted after 5 days of fever. She was deeply jaundiced, leukopenic and thrombocytopenic. Marked elevation of transaminases, hyperbilirubinemia and hypoalbuminemia were observed. She had deranged INR values and prolonged aPTT accompanied with hypofibrinogenemia. She also had splenomegaly. She was positive for dengue IgM. Five days later she became polyuric and CT brain image showed gross generalized cerebral edema. Her conditions deteriorated by day 9, became confused with GCS of 9/15. Her BMAT showed minimal histiocytes. Her serum ferritin level peaked at 13,670.00 µg/mL and her sCD163 and sCD25 values were markedly elevated at 4750.00 ng/mL and 4191.00 pg/mL, respectively. She succumbed to the disease on day 10 and examination of her tissues showed the presence of dengue virus genome in the bone marrow.
    DISCUSSION AND EVALUATION: It is described here, a case of fatal dengue with clinical features of HPS. Though BMAT results did not show the presence of macrophage hemophagocytosis, other laboratory features were consistent with HPS especially marked elevation of ferritin, sCD163 and sCD25. Detection of dengue virus in the patient's bone marrow, fifteen days after the onset of fever was also consistent with the suggestion that the HPS is associated with dengue virus infection.
    CONCLUSIONS: The findings highlight HPS as a possible complication leading to severe dengue and revealed persistent dengue virus infection of the bone marrow. Detection of HPS markers; ferritin, sCD163 and sCD25, therefore, should be considered for early recognition of HPS-associated dengue.
    KEYWORDS: Bone marrow; Dengue; Ferritin; Hemophagocytic syndrome; MAS; Macrophage
    Study site: University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  2. Lau YL, Lai MY, Teoh BT, Abd-Jamil J, Johari J, Sam SS, et al.
    PLoS One, 2015;10(9):e0138694.
    PMID: 26384248 DOI: 10.1371/journal.pone.0138694
    Dengue is usually diagnosed by isolation of the virus, serology or molecular diagnostic methods. Several commercial kits for the diagnosis of dengue are existing, but concerns have arisen regarding to the affordability and performance characteristics of these kits. Hence, the loop-mediated isothermal amplification (LAMP) is potentially ideal to be used especially in resource limited environments. Serum was collected from healthy donors and patients diagnosed with dengue infection. RNA extracted from the serum samples were tested by reverse-transcription-LAMP assay developed based on 3'-NCR gene sequences for DENV 1-4. Results were interpreted by a turbidity meter in real time or visually at the end of the assay. Sensitivity and specificity of RT-LAMP results were calculated and compared to qRT-PCR and ELISA. RT-LAMP is highly sensitive with the detection limit of 10 RNA copies for all serotypes. Dengue virus RNA was detected in all positive samples using RT-LAMP and none of the negative samples within 30-45 minutes. With continuing efforts in the optimization of this assay, RT-LAMP may provide a simple and reliable test for detecting DENV in areas where dengue is prevalent.
  3. Khoo JJ, Chen F, Kho KL, Ahmad Shanizza AI, Lim FS, Tan KK, et al.
    Ticks Tick Borne Dis, 2016 07;7(5):929-937.
    PMID: 27132518 DOI: 10.1016/j.ttbdis.2016.04.013
    Ticks are vectors in the transmission of many important infectious diseases in human and animals. Ticks can be readily found in the semi-forested areas such as the settlements of the indigenous people in Malaysia, the Orang Asli. There is still minimal information available on the bacterial agents associated with ticks found in Malaysia. We performed a survey of the bacterial communities associated with ticks collected from domestic animals found in two Orang Asli villages in Malaysia. We collected 62 ticks, microscopically and molecularly identified as related to Haemaphysalis wellingtoni, Haemaphysalis hystricis and Haemaphysalis bispinosa. Bacterial 16s rRNA hypervariable region (V6) amplicon libraries prepared from the tick samples were sequenced on the Ion Torrent PGM platform. We detected a total of 392 possible bacterial genera after pooling and sequencing 20 samples, indicating a diverse bacterial community profile. Dominant taxa include the potential tick endosymbiont, Coxiella. Other dominant taxa include the tick-associated pathogen, Rickettsia, and environmental bacteria such as Bacillus, Mycobacterium, Sphingomonas and Pseudomonas. Other known tick-associated bacteria were also detected, including Anaplasma, Ehrlichia, Rickettsiella and Wolbachia, albeit at very low abundance. Specific PCR was performed on selected samples to identify Rickettsia and Coxiella. Sequence of Rickettsia felis, which causes spotted fever in human and cats, was identified in one sample. Coxiella endosymbionts were detected in three samples. This study provides the baseline knowledge of the microbiome of ticks in Malaysia, focusing on tick-associated bacteria affecting the Orang Asli communities. The role of the herein found Coxiella and Rickettsia in tick physiology or disease transmission merits further investigation.
  4. Tan KK, Tan YC, Chang LY, Lee KW, Nor'e SS, Yee WY, et al.
    J Infect Dev Ctries, 2017 Jun 01;11(5):420-425.
    PMID: 30943180 DOI: 10.3855/jidc.7598
    INTRODUCTION: Currently available tests have limitations for the identification of Brucella species and strains, and their genetic lineage. The genome sequence of the rpoB gene encoding the β-subunit of DNA-dependent RNA polymerase was investigated for its use in genotyping Brucella melitensis.

    METHODOLOGY: Complete rpoB gene sequences of globally distributed Brucella melitensis strains were analyzed. Single nucleotides polymorphisms (SNPs) of the rpoB gene sequences were identified and used to type Brucella melitensis strains.

    RESULTS: Six DNA polymorphisms were identified, of which two (nucleotides 3201 and 558) were novel. Analysis of the geographical distribution of the strains revealed a spatial clustering pattern with rpoB type 1 representing European and American strains, rpoB type 2 representing European, African, and Asian strains, rpoB type 3 representing Mediterranean strains, and rpoB type 4 representing African (C3201T) and European (C3201T/T558A) strains.

    CONCLUSIONS: We report the discovery of two novel SNPs of rpoB gene that can serve as useful markers for epidemiology and geographical tracking of B. melitensis.

  5. Ng DC, Tan KK, Chin L, Ali MM, Lee ML, Mahmood FM, et al.
    Int J Infect Dis, 2021 Jul;108:347-352.
    PMID: 34087485 DOI: 10.1016/j.ijid.2021.05.073
    OBJECTIVES: To describe the clinical and epidemiological characteristics of children with coronavirus disease 2019 (COVID-19) in the state of Negeri Sembilan, Malaysia in the setting of mandatory hospital isolation and quarantine for all confirmed cases.

    METHODS: A multi-centre, retrospective observational study was performed among children aged ≤12 years with laboratory-proven COVID-19 between 1 February and 31 December 2020.

    RESULTS: In total, 261 children (48.7% males, 51.3% females) were included in this study. The median age was 6 years [interquartile range (IQR) 3-10 years]. One hundred and fifty-one children (57.9%) were asymptomatic on presentation. Among the symptomatic cases, fever was the most common presenting symptom. Two hundred and forty-one (92.3%) cases were close contacts of infected household or extended family members. Twenty-one (8.4%) cases had abnormal radiological findings. All cases were discharged alive without requiring supplemental oxygen therapy or any specific treatment during hospitalization. The median duration of hospitalization was 7 days (IQR 6-10 days). One (2.1%) of the uninfected guardians accompanying a child in quarantine tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) upon discharge.

    CONCLUSIONS: COVID-19 in children was associated with mild symptoms and a good prognosis. Familial clustering was an important epidemiologic feature in the outbreak in Negeri Sembilan. The risk of transmission of SARS-CoV-2 from children to guardians in hospital isolation was minimal despite close proximity.

  6. Tan KK, Azizan NS, Yaacob CN, Che Mat Seri NAA, Samsudin NI, Teoh BT, et al.
    BMC Infect Dis, 2018 04 11;18(1):169.
    PMID: 29642856 DOI: 10.1186/s12879-018-3065-1
    BACKGROUND: A method for rapid detection of dengue virus using the reverse-transcription recombinase polymerase amplification (RT-RPA) was recently developed, evaluated and made ready for deployment. However, reliance solely on the evaluation performed by experienced researchers in a well-structured and well-equipped reference laboratory may overlook the potential intrinsic problems that may arise during deployment of the assay into new application sites, especially for users unfamiliar with the test. Appropriate assessment of this newly developed assay by users who are unfamiliar with the assay is, therefore, vital.

    METHODS: An operational utility test to elucidate the efficiency and effectiveness of the dengue RT-RPA assay was conducted among a group of researchers new to the assay. Nineteen volunteer researchers with different research experience were recruited. The participants performed the RT-RPA assay and interpreted the test results according to the protocol provided. Deviation from the protocol was identified and tabulated by trained facilitators. Post-test questionnaires were conducted to determine the user satisfaction and acceptability of the dengue RT-RPA assay.

    RESULTS: All the participants completed the test and successfully interpreted the results according to the provided instructions, regardless of their research experience. Of the 19 participants, three (15.8%) performed the assay with no deviations and 16 (84.2%) performed the assay with only 1 to 5 deviations. The number of deviations from protocol, however, was not correlated with the user laboratory experience. The accuracy of the results was also not affected by user laboratory experience. The concordance of the assay results against that of the expected was at 89.3%. The user satisfaction towards the RT-RPA protocol and interpretation of results was 90% and 100%, respectively.

    CONCLUSIONS: The dengue RT-RPA assay can be successfully performed by simply following the provided written instructions. Deviations from the written protocols did not adversely affect the outcome of the assay. These suggest that the RT-RPA assay is indeed a simple, robust and efficient laboratory method for detection of dengue virus. Furthermore, high new user acceptance of the RT-RPA assay suggests that this assay could be successfully deployed into new laboratories where RT-RPA was not previously performed.

  7. Tan KK, Zulkifle NI, Sulaiman S, Pang SP, NorAmdan N, MatRahim N, et al.
    BMC Evol. Biol., 2018 04 24;18(1):58.
    PMID: 29699483 DOI: 10.1186/s12862-018-1175-4
    BACKGROUND: Dengue virus type 3 genotype III (DENV3/III) is associated with increased number of severe infections when it emerged in the Americas and Asia. We had previously demonstrated that the DENV3/III was introduced into Malaysia in the late 2000s. We investigated the genetic diversity of DENV3/III strains recovered from Malaysia and examined their phylogenetic relationships against other DENV3/III strains isolated globally.

    RESULTS: Phylogenetic analysis revealed at least four distinct DENV3/III lineages. Two of the lineages (DENV3/III-B and DENV3/III-C) are current actively circulating whereas the DENV3/III-A and DENV3/III-D were no longer recovered since the 1980s. Selection pressure analysis revealed strong evidence of positive selection on a number of amino acid sites in PrM, E, NS1, NS2a, NS2b, NS3, NS4a, and NS5. The Malaysian DENV3/III isolates recovered in the 1980s (MY.59538/1987) clustered into DENV3/III-B, which was the lineage with cosmopolitan distribution consisting of strains actively circulating in the Americas, Africa, and Asia. The Malaysian isolates recovered after the 2000s clustered within DENV3/III-C. This DENV3/III-C lineage displayed a more restricted geographical distribution and consisted of isolates recovered from Asia, denoted as the Asian lineage. Amino acid variation sites in NS5 (NS5-553I/M, NS5-629 T, and NS5-820E) differentiated the DENV3/III-C from other DENV3 viruses. The codon 629 of NS5 was identified as a positively selected site. While the NS5-698R was identified as unique to the genome of DENV3/III-C3. Phylogeographic results suggested that the recent Malaysian DENV3/III-C was likely to have been introduced from Singapore in 2008 and became endemic. From Malaysia, the virus subsequently spread into Taiwan and Thailand in the early part of the 2010s and later reintroduced into Singapore in 2013.

    CONCLUSIONS: Distinct clustering of the Malaysian old and new DENV3/III isolates suggests that the currently circulating DENV3/III in Malaysia did not descend directly from the strains recovered during the 1980s. Phylogenetic analyses and common genetic traits in the genome of the strains and those from the neighboring countries suggest that the Malaysian DENV3/III is likely to have been introduced from the neighboring regions. Malaysia, however, serves as one of the sources of the recent regional spread of DENV3/III-C3 within the Asia region.

  8. Wong CH, Tan TR, Heng HY, Ramesh T, Ting PW, Lee WS, et al.
    Med J Malaysia, 2016 Aug;71(4):186-192.
    PMID: 27770117
    Open disclosure is poorly understood in Malaysia but is an ethical and professional responsibility. The objectives of this study were to determine: (1) the perception of parents regarding the severity of medical error in relation to medication use or diagnosis; (2) the preference of parents for information following the medical error and its relation to severity; and (3) the preference of parents with regards to disciplinary action, reporting, and legal action.
  9. Khoo JJ, Lim FS, Tan KK, Chen FS, Phoon WH, Khor CS, et al.
    J Med Entomol, 2017 09 01;54(5):1444-1448.
    PMID: 28874019 DOI: 10.1093/jme/tjx131
    Spirochetes from the Borrelia genus are known to cause diseases in humans, namely Lyme disease and relapsing fever. These organisms are commonly transmitted to humans by arthropod vectors including ticks, mite, and lice. Here, we report the molecular detection of a Borrelia sp. from a Haemaphysalis hystricis Supino tick collected from wildlife in an Orang Asli settlement in Selangor, Malaysia. Phylogenetic analyses of partial 16s rRNA and flaB gene sequences revealed that the Borrelia sp. is closely related to the relapsing fever group borreliae, Borrelia lonestari, Borrelia miyamotoi, and Borrelia theileri, as well as a number of uncharacterized Borrelia sp. from ticks in Portugal and Japan. To our knowledge, this is the first report of a Borrelia sp. detected in H. hystricis, and in Malaysia. The zoonotic potential of this Borrelia sp. merits further investigation.
  10. Tan KK, Dang DA, Kim KH, Kartasasmita C, Kim HM, Zhang XH, et al.
    Hum Vaccin Immunother, 2018 01 02;14(1):95-105.
    PMID: 29125809 DOI: 10.1080/21645515.2017.1375073
    BACKGROUND: Few studies describe the community-acquired pneumonia (CAP) burden in children in Asia. We estimated the proportion of all CAP hospitalizations in children from nine hospitals across the Republic of Korea (high-income), Indonesia, Malaysia (middle-income), and Vietnam (low/middle-income).

    METHODS: Over a one or two-year period, children <5 years hospitalized with CAP were identified using ICD-10 discharge codes. Cases were matched to standardized definitions of suspected (S-CAP), confirmed (C-CAP), or bacterial CAP (B-CAP) used in a pneumococcal conjugate vaccine efficacy study (COMPAS). Median total direct medical costs of CAP-related hospitalizations were calculated.

    RESULTS: Vietnam (three centers): 7591 CAP episodes were identified with 4.3% (95% confidence interval 4.2;4.4) S-CAP, 3.3% (3.2;3.4) C-CAP and 1.4% (1.3;1.4) B-CAP episodes of all-cause hospitalization in children aged <5 years. The B-CAP case fatality rate (CFR) was 1.3%. Malaysia (two centers): 1027 CAP episodes were identified with 2.7% (2.6;2.9); 2.6% (2.4;2.8); 0.04% (0.04;0.1) due to S-CAP, C-CAP, and B-CAP, respectively. One child with B-CAP died. Indonesia (one center): 960 CAP episodes identified with 18.0% (17.0;19.1); 16.8% (15.8;17.9); 0.3% (0.2;0.4) due to S-CAP, C-CAP, and B-CAP, respectively. The B-CAP CFR was 20%. Korea (three centers): 3151 CAP episodes were identified with 21.1% (20.4;21.7); 11.8% (11.2;12.3); 2.4% (2.1;2.7) due to S-CAP, C-CAP, and B-CAP, respectively. There were no deaths.

    COSTS: CAP-related hospitalization costs were highest for B-CAP episodes: 145.00 (Vietnam) to 1013.3 USD (Korea) per episode.

    CONCLUSION: CAP hospitalization causes an important health and cost burden in all four countries studied (NMRR-12-50-10793).

  11. Zandi K, Lim TH, Rahim NA, Shu MH, Teoh BT, Sam SS, et al.
    BMC Complement Altern Med, 2013 Apr 29;13:91.
    PMID: 23627436 DOI: 10.1186/1472-6882-13-91
    BACKGROUND: Scutellaria baicalensis (S. baicalensis) is one of the traditional Chinese medicinal herbs that have been shown to possess many health benefits. In the present study, we evaluated the in vitro antiviral activity of aqueous extract of the roots of S. baicalensis against all the four dengue virus (DENV) serotypes.

    METHODS: Aqueous extract of S. baicalensis was prepared by microwave energy steam evaporation method (MEGHE™), and the anti-dengue virus replication activity was evaluated using the foci forming unit reduction assay (FFURA) in Vero cells. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to determine the actual dengue virus RNA copy number. The presence of baicalein, a flavonoid known to inhibit dengue virus replication was determined by mass spectrometry.

    RESULTS: The IC(50) values for the S. baicalensis extract on Vero cells following DENV adsorption ranged from 86.59 to 95.19 μg/mL for the different DENV serotypes. The IC(50) values decreased to 56.02 to 77.41 μg/mL when cells were treated with the extract at the time of virus adsorption for the different DENV serotypes. The extract showed potent direct virucidal activity against extracellular infectious virus particles with IC(50) that ranged from 74.33 to 95.83 μg/mL for all DENV serotypes. Weak prophylactic effects with IC(50) values that ranged from 269.9 to 369.8 μg/mL were noticed when the cells were pre-treated 2 hours prior to virus inoculation. The concentration of baicalein in the S. baicalensis extract was ~1% (1.03 μg/gm dried extract).

    CONCLUSIONS: Our study demonstrates the in vitro anti-dengue virus replication property of S. baicalensis against all the four DENV serotypes investigated. The extract reduced DENV infectivity and replication in Vero cells. The extract was rich in baicalein, and could be considered for potential development of anti-DENV therapeutics.

  12. Ng DC, Tan KK, Liew CH, Low YW, Chin L, Jamil MB, et al.
    Pediatr Int, 2023;65(1):e15565.
    PMID: 37368506 DOI: 10.1111/ped.15565
    BACKGROUND: This study aimed to describe the clinical characteristics and severity of young infants hospitalized with COVID-19 and study the relationship between breastfeeding and maternal COVID-19 vaccination on the severity of COVID-19.

    METHODS: A retrospective, observational study was performed among infants aged 6 months and below hospitalized for COVID-19 in a tertiary state hospital in Malaysia between February 1 and April 30, 2022. The primary outcome was "serious disease," defined as pneumonia requiring respiratory support or dehydration with warning signs. Multivariate logistic regression was used to determine independent predictors for serious disease.

    RESULTS: A total of 102 infants were included in the study; 53.9% were males with a median age of 11 weeks (interquartile range: 5-20 weeks). Sixteen patients (15.7%) had pre-existing comorbidities, including preterm birth. Fever was the most common presenting symptom (82.4%), followed by cough (53.9%), and rhinorrhea (31.4%). Forty-one infants (40.2%) presented with serious disease, warranting either respiratory support or intravenous fluid therapy for dehydration. Recent maternal COVID-19 vaccination was associated with a reduced risk of serious disease on univariate analysis but was not significant after multivariate adjustment (adjusted odds ratio [aOR] 0.39; 95% CI: 0.14-1.11; p = 0.08). Exclusive breastfeeding was protective against serious COVID-19 in young infants, independent of other confounding factors (aOR 0.21, 95% CI: 0.06-0.71; p = 0.01).

    CONCLUSION: COVID-19 is a serious disease with non-specific clinical manifestations in young infants. Exclusive breastfeeding could play an important protective role.

  13. Muhammad Ismail HI, Tan KK, Lee YL, Pau WS, Razali KA, Mohamed T, et al.
    Emerg Infect Dis, 2011 Apr;17(4):708-10.
    PMID: 21470467 DOI: 10.3201/eid1704.101212
    To determine effects of pandemic (H1N1) 2009 on children in the tropics, we examined characteristics of children hospitalized for this disease in Malaysia. Of 1,362 children, 51 (3.7%) died, 46 of whom were in an intensive care unit. Although disease was usually mild, ≥ 1 concurrent conditions were associated with higher death rates.
  14. Yip JQ, Oo A, Ng YL, Chin KL, Tan KK, Chu JJH, et al.
    Virol J, 2024 Dec 20;21(1):327.
    PMID: 39707400 DOI: 10.1186/s12985-024-02597-3
    The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has profoundly impacted global healthcare systems and spurred extensive research efforts over the past three years. One critical aspect of the disease is the intricate interplay between the virus and the host immune response, particularly the role of inflammatory gene expression in severe COVID-19. While numerous previous studies have explored the role of genetic polymorphisms in COVID-19, research specifically focusing on inflammatory genes and their associations with disease severity remains limited. This review explores the relationship between severe COVID-19 outcomes and genetic polymorphisms within key inflammatory genes. By investigating the impact of genetic variations on immune responses, which include cytokine production and downstream signalling pathways, we aim to provide a comprehensive overview of how genetic polymorphisms contribute to the variability in disease presentation. Through an in-depth analysis of existing literature, we shed light on potential therapeutic targets and personalized approaches that may enhance our understanding of disease pathogenesis and treatment strategies.
  15. Lim FS, Koh MT, Tan KK, Chan PC, Chong CY, Shung Yehudi YW, et al.
    BMC Infect Dis, 2014;14:530.
    PMID: 25278086 DOI: 10.1186/1471-2334-14-530
    BACKGROUND: The immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines were evaluated among infants from Singapore and Malaysia, where PHiD-CV has been licensed.
    METHODS: In the primary vaccination phase, 298 infants from Singapore and 168 infants from Malaysia were randomised to receive the Phase III Clinical (Clin) or the Commercial (Com) lot of PHiD-CV at 2, 3, and 5 months of age. In the booster vaccination phase, 238 toddlers from Singapore received one dose of the PHiD-CV Commercial lot at 18-21 months of age. Immune responses to pneumococcal polysaccharides were measured using 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and functional opsonophagocytic activity (OPA) assay and to protein D, using ELISA.
    RESULTS: Immune responses induced by primary vaccination with the PHiD-CV Commercial lot were non-inferior to the Phase III Clinical lot in terms of adjusted antibody geometric mean concentration (GMC) ratios for each vaccine pneumococcal serotype and protein D. For each vaccine pneumococcal serotype, ≥93.6% and ≥88.5% of infants from Malaysia and Singapore had post-primary vaccination antibody concentrations ≥0.2 μg/mL and OPA titres ≥8, in the Clin and Com groups, respectively. For each vaccine pneumococcal serotype, ≥60.8% and ≥98.2% of toddlers from Singapore had pre- and post-booster antibody concentrations ≥0.2 μg/mL, in the Clin and Com groups, respectively. All children, except one, had measurable anti-protein D antibodies and the primary and booster doses of the co-administered vaccines were immunogenic. The incidence of each grade 3 solicited symptom was ≤11.1% in both study phases. No serious adverse events considered causally related to vaccination were reported throughout the study.
    CONCLUSIONS: PHiD-CV given as three-dose primary vaccination to infants in Singapore and Malaysia and booster vaccination to toddlers in Singapore was shown to be immunogenic with a clinically acceptable-safety profile.This study has been registered at http://www.clinicaltrials.govNCT00808444 and NCT01119625.
  16. Teoh BT, Sam SS, Tan KK, Johari J, Shu MH, Danlami MB, et al.
    BMC Evol. Biol., 2013;13:213.
    PMID: 24073945 DOI: 10.1186/1471-2148-13-213
    Recurring dengue outbreaks occur in cyclical pattern in most endemic countries. The recurrences of dengue virus (DENV) infection predispose the population to increased risk of contracting the severe forms of dengue. Understanding the DENV evolutionary mechanism underlying the recurring dengue outbreaks has important implications for epidemic prediction and disease control.
  17. Tan KK, Tan YC, Chang LY, Lee KW, Nore SS, Yee WY, et al.
    BMC Genomics, 2015;16:93.
    PMID: 25888205 DOI: 10.1186/s12864-015-1294-x
    Brucellosis is an important zoonotic disease that affects both humans and animals. We sequenced the full genome and characterised the genetic diversity of two Brucella melitensis isolates from Malaysia and the Philippines. In addition, we performed a comparative whole-genome single nucleotide polymorphism (SNP) analysis of B. melitensis strains collected from around the world, to investigate the potential origin and the history of the global spread of B. melitensis.
  18. Teoh BT, Chin KL, Samsudin NI, Loong SK, Sam SS, Tan KK, et al.
    BMC Infect Dis, 2020 Dec 11;20(1):947.
    PMID: 33308203 DOI: 10.1186/s12879-020-05585-4
    BACKGROUND: Early detection of Zika virus (ZIKV) infection during the viremia and viruria facilitates proper patient management and mosquito control measurement to prevent disease spread. Therefore, a cost-effective nucleic acid detection method for the diagnosis of ZIKV infection, especially in resource-deficient settings, is highly required.

    METHODS: In the present study, a single-tube reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for the detection of both the Asian and African-lineage ZIKV. The detection limit, strain coverage and cross-reactivity of the ZIKV RT-LAMP assay was evaluated. The sensitivity and specificity of the RT-LAMP were also evaluated using a total of 24 simulated clinical samples. The ZIKV quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was used as the reference assay.

    RESULTS: The detection limit of the RT-LAMP assay was 3.73 ZIKV RNA copies (probit analysis, P ≤ 0.05). The RT-LAMP assay detected the ZIKV genomes of both the Asian and African lineages without cross-reacting with other arthropod-borne viruses. The sensitivity and specificity of the RT-LAMP assay were 90% (95% CI = 59.6-98.2) and 100% (95% CI = 78.5-100.0), respectively. The RT-LAMP assay detected ZIKV genome in 9 of 24 (37.5%) of the simulated clinical samples compared to 10 of 24 (41.7%) by qRT-PCR assay with a high level of concordance (κ = 0.913, P 

  19. Tan KK, Tiong V, Tan JY, Wong JE, Teoh BT, Abd-Jamil J, et al.
    Trop Biomed, 2021 Sep 01;38(3):283-288.
    PMID: 34362871 DOI: 10.47665/tb.38.3.069
    Various methods have been developed for rapid and high throughput full genome sequencing of SARS-CoV-2. Here, we described a protocol for targeted multiplex full genome sequencing of SARS-CoV-2 genomic RNA directly extracted from human nasopharyngeal swabs using the Ion Personal Genome Machine (PGM). This protocol involves concomitant amplification of 237 gene fragments encompassing the SARS-CoV-2 genome to increase the abundance and yield of viral specific sequencing reads. Five complete and one near-complete genome sequences of SARS-CoV-2 were generated with a single Ion PGM sequencing run. The sequence coverage analysis revealed two amplicons (positions 13 751-13 965 and 23 941-24 106), which consistently gave low sequencing read coverage in all isolates except 4Apr20-64- Hu. We analyzed the potential primer binding sites within these low covered regions and noted that the 4Apr20-64-Hu possess C at positions 13 730 and 23 929, whereas the other isolates possess T at these positions. The genome nucleotide variations observed suggest that the naturally occurring variations present in the actively circulating SARS-CoV-2 strains affected the performance of the target enrichment panel of the Ion AmpliSeq™ SARS CoV 2 Research Panel. The possible impact of other genome nucleotide variations warrants further investigation, and an improved version of the Ion AmpliSeq™ SARS CoV 2 Research Panel, hence, should be considered.
  20. Tan KK, Zulkifle NI, Abd-Jamil J, Sulaiman S, Yaacob CN, Azizan NS, et al.
    Infect Genet Evol, 2017 Oct;54:271-275.
    PMID: 28698156 DOI: 10.1016/j.meegid.2017.07.008
    Dengue is hyperendemic in most of Southeast Asia. In this region, all four dengue virus serotypes are persistently present. Major dengue outbreak cycle occurs in a cyclical pattern involving the different dengue virus serotypes. In Malaysia, since the 1980s, the major outbreak cycles have involved dengue virus type 3 (DENV3), dengue virus type 1 (DENV1) and dengue virus type 2 (DENV2), occurring in that order (DENV3/DENV1/DENV2). Only limited information on the DENV3 cycles, however, have been described. In the current study, we examined the major outbreak cycle involving DENV3 using data from 1985 to 2016. We examined the genetic diversity of DENV3 isolates obtained during the period when DENV3 was the dominant serotype and during the inter-dominant transmission period. Results obtained suggest that the typical DENV3/DENV1/DENV2 cyclical outbreak cycle in Malaysia has recently been disrupted. The last recorded major outbreak cycle involving DENV3 occurred in 2002, and the expected major outbreak cycle involving DENV3 in 2006-2012 did not materialize. DENV genome analyses revealed that DENV3 genotype II (DENV3/II) was the predominant DENV3 genotype (67%-100%) recovered between 1987 and 2002. DENV3 genotype I (DENV3/I) emerged in 2002 followed by the introduction of DENV3 genotype III (DENV3/III) in 2008. These newly emerged DENV3 genotypes replaced DENV3/II, but there was no major upsurge of DENV3 cases that accompanied the emergence of these viruses. DENV3 remained in the background of DENV1 and DENV2 until now. Virus genome sequence analysis suggested that intrinsic differences within the different dengue virus genotypes could have influenced the transmission efficiency of DENV3. Further studies and continuous monitoring of the virus are needed for better understanding of the DENV transmission dynamics in hyperendemic regions.
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