Displaying publications 1 - 20 of 56 in total

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  1. Zulkefli NJ, Mariappan V, Vellasamy KM, Chong CW, Thong KL, Ponnampalavanar S, et al.
    PeerJ, 2016;4:e1802.
    PMID: 26998408 DOI: 10.7717/peerj.1802
    Background. Central intermediary metabolism (CIM) in bacteria is defined as a set of metabolic biochemical reactions within a cell, which is essential for the cell to survive in response to environmental perturbations. The genes associated with CIM are commonly found in both pathogenic and non-pathogenic strains. As these genes are involved in vital metabolic processes of bacteria, we explored the efficiency of the genes in genotypic characterization of Burkholderia pseudomallei isolates, compared with the established pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) schemes. Methods. Nine previously sequenced B. pseudomallei isolates from Malaysia were characterized by PFGE, MLST and CIM genes. The isolates were later compared to the other 39 B. pseudomallei strains, retrieved from GenBank using both MLST and sequence analysis of CIM genes. UniFrac and hierachical clustering analyses were performed using the results generated by both MLST and sequence analysis of CIM genes. Results. Genetic relatedness of nine Malaysian B. pseudomallei isolates and the other 39 strains was investigated. The nine Malaysian isolates were subtyped into six PFGE profiles, four MLST profiles and five sequence types based on CIM genes alignment. All methods demonstrated the clonality of OB and CB as well as CMS and THE. However, PFGE showed less than 70% similarity between a pair of morphology variants, OS and OB. In contrast, OS was identical to the soil isolate, MARAN. To have a better understanding of the genetic diversity of B. pseudomallei worldwide, we further aligned the sequences of genes used in MLST and genes associated with CIM for the nine Malaysian isolates and 39 B. pseudomallei strains from NCBI database. Overall, based on the CIM genes, the strains were subtyped into 33 profiles where majority of the strains from Asian countries were clustered together. On the other hand, MLST resolved the isolates into 31 profiles which formed three clusters. Hierarchical clustering using UniFrac distance suggested that the isolates from Australia were genetically distinct from the Asian isolates. Nevertheless, statistical significant differences were detected between isolates from Malaysia, Thailand and Australia. Discussion. Overall, PFGE showed higher discriminative power in clustering the nine Malaysian B. pseudomallei isolates and indicated its suitability for localized epidemiological study. Compared to MLST, CIM genes showed higher resolution in distinguishing those non-related strains and better clustering of strains from different geographical regions. A closer genetic relatedness of Malaysian isolates with all Asian strains in comparison to Australian strains was observed. This finding was supported by UniFrac analysis which resulted in geographical segregation between Australia and the Asian countries.
  2. Zulkefli NJ, Teh CSJ, Mariappan V, Ngoi ST, Vadivelu J, Ponnampalavanar S, et al.
    PLoS One, 2021;16(12):e0261382.
    PMID: 34910764 DOI: 10.1371/journal.pone.0261382
    Burkholderia pseudomallei (B. pseudomallei) is an intracellular pathogen that causes melioidosis, a life-threatening infection in humans. The bacterium is able to form small colony variants (SCVs) as part of the adaptive features in response to environmental stress. In this study, we characterize the genomic characteristics, antimicrobial resistance (AMR), and metabolic phenotypes of B. pseudomallei SCV and wild type (WT) strains. Whole-genome sequence analysis was performed to characterize the genomic features of two SCVs (CS and OS) and their respective parental WT strains (CB and OB). Phylogenetic relationship between the four draft genomes in this study and 19 publicly available genomes from various countries was determined. The four draft genomes showed a close phylogenetic relationship with other genomes from Southeast Asia. Broth microdilution and phenotype microarray were conducted to determine the AMR profiles and metabolic features (carbon utilization, osmolytes sensitivity, and pH conditions) of all strains. The SCV strains exhibited identical AMR phenotype with their parental WT strains. A limited number of AMR-conferring genes were identified in the B. pseudomallei genomes. The SCVs and their respective parental WT strains generally shared similar carbon-utilization profiles, except for D,L-carnitine (CS), g-hydroxybutyric acid (OS), and succinamic acid (OS) which were utilized by the SCVs only. No difference was observed in the osmolytes sensitivity of all strains. In comparison, WT strains were more resistant to alkaline condition, while SCVs showed variable growth responses at higher acidity. Overall, the genomes of the colony morphology variants of B. pseudomallei were largely identical, and the phenotypic variations observed among the different morphotypes were strain-specific.
  3. Yeo AS, Rathakrishnan A, Wang SM, Ponnampalavanar S, Manikam R, Sathar J, et al.
    Biomed Res Int, 2015;2015:420867.
    PMID: 25815314 DOI: 10.1155/2015/420867
    Dengue virus infection is a common tropical disease which often occurs without being detected. These asymptomatic cases provide information in relation to the manifestation of immunological aspects. In this study, we developed an ELISA method to compare neutralizing effects of dengue prM and E antibodies between dengue patients and their asymptomatic household members. Recombinant D2 premembrane (prM) was constructed, cloned, and tested for antigenicity. The recombinant protein was purified and tested with controls by using an indirect ELISA method. Positive dengue serum samples with their asymptomatic pair were then carried out onto the developed ELISA. In addition, commercially available recombinant envelope (E) protein was used to develop an ELISA which was tested with the same set of serum samples in the prM ELISA. Asymptomatic individuals showed preexisting heterotypic neutralizing antibodies. The recombinant prM was antigenically reactive in the developed ELISA. Dengue patients had higher prM and E antibodies compared to their household members. Our study highlights the neutralizing antibodies levels with respect to dengue prM and E between dengue patients and asymptomatic individuals.
  4. Yap PSX, Chong CW, Ponnampalavanar S, Ramli R, Harun A, Tengku Jamaluddin TZM, et al.
    PeerJ, 2023;11:e16393.
    PMID: 38047021 DOI: 10.7717/peerj.16393
    BACKGROUND: The high burden of extended-spectrum beta-lactamase-producing (ESBL)-producing Enterobacterales worldwide, especially in the densely populated South East Asia poses a significant threat to the global transmission of antibiotic resistance. Molecular surveillance of ESBL-producing pathogens in this region is vital for understanding the local epidemiology, informing treatment choices, and addressing the regional and global implications of antibiotic resistance.

    METHODS: Therefore, an inventory surveillance of the ESBL-Escherichia coli (ESBL-EC) isolates responsible for infections in Malaysian hospitals was conducted. Additionally, the in vitro efficacy of flomoxef and other established antibiotics against ESBL-EC was evaluated.

    RESULTS: A total of 127 non-repetitive ESBL-EC strains isolated from clinical samples were collected during a multicentre study performed in five representative Malaysian hospitals. Of all the isolates, 33.9% were isolated from surgical site infections and 85.8% were hospital-acquired infections. High rates of resistance to cefotaxime (100%), cefepime (100%), aztreonam (100%) and trimethoprim-sulfamethoxazole (100%) were observed based on the broth microdilution test. Carbapenems remained the most effective antibiotics against the ESBL-EC, followed by flomoxef. Antibiotic resistance genes were identified by PCR. The blaCTX-M-1 was the most prevalent ESBL gene, with 28 isolates (22%) harbouring blaCTX-M-1 only, 27 isolates (21.3%) co-harbouring blaCTX-M-1 and blaTEM, and ten isolates (7.9%) co-harbouring blaCTX-M-1, blaTEM and blaSHV. A generalised linear model showed significant antibacterial activity of imipenem against different types of infection. Besides carbapenems, this study also demonstrated a satisfactory antibacterial activity of flomoxef (81.9%) on ESBL-EC, regardless of the types of ESBL genes.

  5. Wan KS, Tok PSK, Yoga Ratnam KK, Aziz N, Isahak M, Ahmad Zaki R, et al.
    PLoS One, 2021;16(4):e0249394.
    PMID: 33852588 DOI: 10.1371/journal.pone.0249394
    INTRODUCTION: The reporting of Coronavirus Disease 19 (COVID-19) mortality among healthcare workers highlights their vulnerability in managing the COVID-19 pandemic. Some low- and middle-income countries have highlighted the challenges with COVID-19 testing, such as inadequate capacity, untrained laboratory personnel, and inadequate funding. This article describes the components and implementation of a healthcare worker surveillance programme in a designated COVID-19 teaching hospital in Malaysia. In addition, the distribution and characteristics of healthcare workers placed under surveillance are described.

    MATERIAL AND METHODS: A COVID-19 healthcare worker surveillance programme was implemented in University Malaya Medical Centre. The programme involved four teams: contact tracing, risk assessment, surveillance and outbreak investigation. Daily symptom surveillance was conducted over fourteen days for healthcare workers who were assessed to have low-, moderate- and high-risk of contracting COVID-19. A cross-sectional analysis was conducted for data collected over 24 weeks, from the 6th of March 2020 to the 20th of August 2020.

    RESULTS: A total of 1,174 healthcare workers were placed under surveillance. The majority were females (71.6%), aged between 25 and 34 years old (64.7%), were nursing staff (46.9%) and had no comorbidities (88.8%). A total of 70.9% were categorised as low-risk, 25.7% were moderate-risk, and 3.4% were at high risk of contracting COVID-19. One-third (35.2%) were symptomatic, with the sore throat (23.6%), cough (19.8%) and fever (5.0%) being the most commonly reported symptoms. A total of 17 healthcare workers tested positive for COVID-19, with a prevalence of 0.3% among all the healthcare workers. Risk category and presence of symptoms were associated with a positive COVID-19 test (p<0.001). Fever (p<0.001), cough (p = 0.003), shortness of breath (p = 0.015) and sore throat (p = 0.002) were associated with case positivity.

    CONCLUSION: COVID-19 symptom surveillance and risk-based assessment have merits to be included in a healthcare worker surveillance programme to safeguard the health of the workforce.

  6. Teh CSJ, Yap PSX, Zulkefli NJ, Subramaniam P, Sit PS, Kong ZX, et al.
    Transbound Emerg Dis, 2021 Jan 27.
    PMID: 33506647 DOI: 10.1111/tbed.14005
    Burkholderia pseudomallei, a Gram-negative bacterial pathogen that causes melioidosis, is of public health importance in endemic areas including Malaysia. An investigation of the molecular epidemiology links of B. pseudomallei would contribute to better understanding of the clonal relationships, transmission dynamics and evolutionary change. Multi-locus sequence typing (MLST) of 45 clinical B. pseudomallei isolates collected from sporadic meliodosis cases in Malaysia was performed. In addition, a total of 449 B. pseudomallei Malaysian strains submitted to the MLST database from 1964 until 2019 were included in the temporal analysis to determine the endemic sequence types (STs), emergence and re-emergence of ST(s). In addition, strain-specific distribution was evaluated using BURST tool. Genotyping of 45 clinical strains were resolved into 12 STs and the majority were affiliated with ST46 (n=11) and ST1342 (n=7). Concomitantly, ST46 was the most prevalent ST in Malaysia which first reported in 1964. All the Malaysian B. pseudomallei strains were resolved into 76 different STs with 36 of them uniquely present only in Malaysia. ST1342 was most closely related to ST1034, in which both STs were unique to Malaysia and first isolated from soil samples in Pahang, a state in Malaysia. The present study revealed a high diversity of B. pseudomallei in Malaysia. Localised evolution giving rise to the emergence of new STs was observed, suggesting that host and environmental factors play a crucial role in the evolutionary changes of B. pseudomallei.
  7. Tay ST, Lotfalikhani A, Sabet NS, Ponnampalavanar S, Sulaiman S, Na SL, et al.
    Mycopathologia, 2014 Oct;178(3-4):307-14.
    PMID: 25022264 DOI: 10.1007/s11046-014-9778-9
    BACKGROUND: Candida nivariensis and C. bracarensis have been recently identified as emerging yeast pathogens which are phenotypically indistinguishable from C. glabrata. However, there is little data on the prevalence and antifungal susceptibilities of these species.

    OBJECTIVE: This study investigated the occurrence of C. nivariensis and C. bracarensis in a culture collection of 185 C. glabrata isolates at a Malaysian teaching hospital.

    METHODS: C. nivariensis was discriminated from C. glabrata using a PCR assay as described by Enache-Angoulvant et al. (J Clin Microbiol 49:3375-9, 2011). The identity of the isolates was confirmed by sequence analysis of the D1D2 domain and internal transcribed spacer region of the yeasts. The isolates were cultured on Chromogenic CHROMagar Candida (®) agar (Difco, USA), and their biochemical and enzymic profiles were determined. Antifungal susceptibilities of the isolates against amphotericin B, fluconazole, voriconazole and caspofungin were determined using E tests. Clotrimazole MICs were determined using a microbroth dilution method.

    RESULTS: There was a low prevalence (1.1 %) of C. nivariensis in our culture collection of C. glabrata. C. nivariensis was isolated from a blood culture and vaginal swab of two patients. C. nivariensis grew as white colonies on Chromogenic agar and demonstrated few positive reactions using biochemical tests. Enzymatic profiles of the C. nivariensis isolates were similar to that of C. glabrata. The isolates were susceptible to amphotericin B, fluconazole, voriconazole and caspofungin. Clotrimazole resistance is suspected in one isolate.

    CONCLUSION: This study reports for the first time the emergence of C. nivariensis in our clinical setting.

  8. Tan HY, Yong YK, Andrade BB, Shankar EM, Ponnampalavanar S, Omar SF, et al.
    AIDS, 2015 Feb 20;29(4):421-31.
    PMID: 25565499 DOI: 10.1097/QAD.0000000000000557
    Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a substantial problem in HIV/TB coinfected patients commencing antiretroviral therapy (ART). The immunopathogenesis of TB-IRIS includes increased production of proinflammatory chemokines and cytokines, including interleukin-18, which is a signature cytokine of the nucleotide-binding domain and leucine-rich repeat pyrin containing protein-3 inflammasome. We compared plasma levels of interleukin-18 and other biomarkers of monocyte/macrophage activation in the prediction and characterization of TB-IRIS.
  9. Tan HY, Yong YK, Lim SH, Ponnampalavanar S, Omar SF, Pang YK, et al.
    Sex Health, 2014 Dec;11(6):532-9.
    PMID: 25200957 DOI: 10.1071/SH14093
    Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication of antiretroviral therapy (ART) in countries with high rates of endemic TB, but data from South-East Asia are incomplete. Identification of prevalence, risk factors and treatment outcomes of TB-IRIS in Malaysia was sought.

    METHODS: A 3-year retrospective study was conducted among TB-HIV co-infected patients treated at the University of Malaya Medical Centre. Simple and adjusted logistic regressions were used to identify the predictors for TB-IRIS while Cox regression was used to assess the influence of TB-IRIS on long-term CD4 T-cell recovery.

    RESULTS: One hundred and fifty-three TB-HIV patients were enrolled, of whom 106 had received both anti-TB treatment (ATT) and ART. The median (IQR) baseline CD4 T-cell count was 52 cells μL(-1) (13-130 cells μL(-1)). Nine of 96 patients (9.4%) developed paradoxical TB-IRIS and eight developed unmasking TB-IRIS, at a median (IQR) time of 27 (12-64) and 19 (14-65) days, respectively. In adjusted logistic regression analysis, only disseminated TB was predictive of TB-IRIS [OR: 10.7 (95% CI: 1.2-94.3), P=0.032]. Mortality rates were similar for TB-IRIS (n=1, 5.9%) and non-TB-IRIS (n=5, 5.7%) patients and CD4 T-cell recovery post-ART was not different between the two groups (P=0.363).

    CONCLUSION: Disseminated TB was a strong independent predictor of TB-IRIS in Malaysian HIV-TB patients after commencing ART. This finding underscores the role of a high pathogen load in the pathogenesis of TB-IRIS; so interventions that reduce pathogen load before ART may benefit HIV patients with disseminated TB.

  10. Sunil M, Hieu HQ, Arjan Singh RS, Ponnampalavanar S, Siew KSW, Loch A
    Ann Clin Microbiol Antimicrob, 2019 Dec 17;18(1):43.
    PMID: 31847847 DOI: 10.1186/s12941-019-0341-x
    BACKGROUND: Staphylococcus has replaced streptococcus as the most common cause of infective endocarditis (IE) in developed health care systems. The trend in developing countries is less clear.

    AIM: To examine the epidemiological trends of infective endocarditis in a developing nation.

    METHODS: Single-centre, retrospective study of patients admitted with IE to a tertiary hospital in Malaysia over a 12-year period.

    RESULTS: The analysis included 182 patients (n = 153 Duke's definite IE, n = 29 possible IE). The mean age was 51 years. Rheumatic heart disease was present in 42%, while 7.6% were immunocompromised. IE affected native valves in 171 (94%) cases. Health-care associated IE (HCAIE) was recorded in 68 (37.4%). IE admission rates increased from 25/100,000 admissions (2012) to 59/100,000 admissions (2017). At least one major complication on admission was detected in 59 (32.4%) patients. Left-sided IE was more common than right-sided IE [n = 159 (87.4%) vs. n = 18 (9.9%)]. Pathogens identified by blood culture were staphylococcus group [n = 58 (40.8%)], streptococcus group [n = 51 (35.9%)] and Enterococcus species [n = 13 (9.2%)]. staphylococcus infection was highest in the HCAIE group. In-hospital death occurred in 65 (35.7%) patients. In-hospital surgery was performed for 36 (19.8%) patients. At least one complication was documented in 163 (85.7%).

    CONCLUSION: Staphylococcus is the new etiologic champion, reflecting the transition of the healthcare system. Streptococcus is still an important culprit organism. The incidence rate of IE appears to be increasing. The rate of patients with underlying rheumatic heart disease is still high.

  11. Sulaiman H, Ismail MD, Jalalonmuhali M, Atiya N, Ponnampalavanar S
    Malar J, 2014;13:341.
    PMID: 25176417 DOI: 10.1186/1475-2875-13-341
    This case report describes a case of presumed acute myocardial infarction in a returned traveler who was later diagnosed to have severe malaria. Emergency coronary angiography was normal and subsequent peripheral blood film was positive for Plasmodium falciparum.
  12. Sulaiman H, Ponnampalavanar S, Mun KS, Italiano CM
    BMC Infect Dis, 2013 Nov 09;13:527.
    PMID: 24209898 DOI: 10.1186/1471-2334-13-527
    BACKGROUND: Infections due to Mycobacterium tuberculosis, Burkholderia pseudomallei and non-typhoidal Salmonella cause significant morbidity and mortality throughout the world. These intracellular pathogens share some common predisposing factors and clinical features. Co-infection with two of these organisms has been reported previously but, to our knowledge, this is the first time that infection with all three has been reported in one person.

    CASE PRESENTATION: In September 2010, a 58-year-old diabetic Malaysian male presented with fever and a fluctuant mass on the right side of his neck. B. pseudomallei was isolated from an aspirate of this lesion and there was radiological evidence of disseminated infection in the liver and spleen. The recurrence of clinical symptoms over ensuing months prompted further aspiration and biopsy of a cervical abscess and underlying lymph nodes. Salmonella enterica serovar Stanley and then M. tuberculosis were identified from these specimens by culture and molecular methods. The patient responded to targeted medical management of each of these infections.

    CONCLUSION: In endemic settings, a high index of suspicion and adequate tissue sampling are imperative in identifying these pathogenic organisms. Diabetes was identified as a predisposing factor in this case while our understanding of other potential risk factors is evolving.

  13. Subakir H, Chong YM, Chan YF, Hasan MS, Jamaluddin MFH, Pang YK, et al.
    J Med Microbiol, 2020 Jan;69(1):49-51.
    PMID: 31750812 DOI: 10.1099/jmm.0.001108
    Introduction.Burkholderia pseudomallei (melioidosis) is an important cause of community-acquired pneumonia (CAP) in the tropics. Selective medium is recommended for laboratory diagnosis with non-sterile respiratory samples, while PCR is not routinely used due to variable reported performance. The effectiveness of these diagnostic modalities varies by site.Aim. To compare selective media and real-time PCR (qPCR) with routine media in detecting B. pseudomallei in CAP respiratory samples in a low-incidence setting in Kuala Lumpur, Malaysia.Methodology. Respiratory samples were routinely cultured on blood, chocolate and MacConkey agar (RESP-ROUTINE), and compared to culture on selective Ashdown medium (RESP-SELECTIVE) and qPCR. The gold standard was routine culture of B. pseudomallei from any site (ALL-ROUTINE).Results.B. pseudomallei was detected in 8/204 (3.9 %) samples. Overall sensitivity rates differed (P=0.03) for qPCR (100%), RESP-SELECTIVE (87.5%) and RESP-ROUTINE (50%). There was a trend towards lower median days to positive culture for RESP-SELECTIVE (1 day) compared to RESP-ROUTINE (2 days, P=0.08) and ALL-ROUTINE (2 days, P=0.06). Reagent costs for each additional detection were USD59 for RESP-SELECTIVE and USD354 for PCR.Conclusions. In a low-incidence setting, selective culture of respiratory samples on Ashdown was more sensitive and allowed quicker identification than routine media, at reasonable cost. Blood cultures are critical, confirming four cases missed by routine respiratory culture. Selective medium is useful in early pneumonia (pre-sepsis) and resource-limited settings where blood cultures are infrequently done. Real-time PCR is costly, but highly sensitive and useful for high-risk patients with diabetes, cancer or immunosuppressants, or requiring ventilation or intensive care.
  14. Sit PS, Teh CS, Idris N, Sam IC, Syed Omar SF, Sulaiman H, et al.
    BMC Infect Dis, 2017 04 13;17(1):274.
    PMID: 28407796 DOI: 10.1186/s12879-017-2384-y
    BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an established pathogen that causes hospital- and community-acquired infections worldwide. The prevalence rate of MRSA infections were reported to be the highest in Asia. As there is limited epidemiological study being done in Malaysia, this study aimed to determine the prevalence of MRSA infection and the molecular characteristics of MRSA bacteraemia.

    METHODS: Two hundred and nine MRSA strains from year 2011 to 2012 were collected from a tertiary teaching hospital in Malaysia. The strains were characterized by antimicrobial susceptibility testing, staphylococcal cassette chromosome mec (SCCmec) typing, detection of Panton-Valentine leukocidin (PVL) gene, multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Patient's demographic and clinical data were collected and correlated with molecular data by statistical analysis.

    RESULTS: Male gender and patient >50 years of age (p 

  15. Sit PS, Teh CSJ, Idris N, Ponnampalavanar S
    Infect Genet Evol, 2018 04;59:132-141.
    PMID: 29421224 DOI: 10.1016/j.meegid.2018.01.031
    Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a serious infection that can result in significant morbidity and mortality. A retrospective cohort study was conducted to determine the predictors of mortality in patient with MRSA bacteremia correlating with clinical, phenotypic and genotypic characteristics of the relevant strains. Most of the bacteremia cases were healthcare-associated (P 
  16. Sam IC, Kamarulzaman A, Ong GS, Veriah RS, Ponnampalavanar S, Chan YF, et al.
    Trop Biomed, 2010 Aug;27(2):343-7.
    PMID: 20962735
    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus which causes fever, rash, and arthralgia. In the past, life-threatening complications were very rarely reported. However, during the recent worldwide outbreaks, there have been several reports of unusually severe complications and deaths. Malaysia is experiencing a nationwide outbreak of CHIKV, with over 10 000 patients affected since April 2008. We report the first case of culture-confirmed CHIKV-associated death in Malaysia, in a patient with fever, rash, acute exacerbation of pre-existing heart failure, rhabdomyolysis, and multiple organ failure. CHIKV infections may cause atypical, severe or fatal presentations.
  17. Sam IC, Chong YM, Abdullah A, Fu JYL, Hasan MS, Jamaluddin FH, et al.
    J Med Virol, 2021 Nov 10.
    PMID: 34757638 DOI: 10.1002/jmv.27441
    Malaysia has experienced three waves of coronavirus disease 2019 (COVID-19) as of March 31, 2021. We studied the associated molecular epidemiology and SARS-CoV-2 seroprevalence during the third wave. We obtained 60 whole-genome SARS-CoV-2 sequences between October 2020 and January 2021 in Kuala Lumpur/Selangor and analyzed 989 available Malaysian sequences. We tested 653 residual serum samples collected between December 2020 to April 2021 for anti-SARS-CoV-2 total antibodies, as a proxy for population immunity. The first wave (January 2020) comprised sporadic imported cases from China of early Pango lineages A and B. The second wave (March-June 2020) was associated with lineage B.6. The ongoing third wave (from September 2020) was propagated by a state election in Sabah. It is due to lineage B.1.524 viruses containing spike mutations D614G and A701V. Lineages B.1.459, B.1.470, and B.1.466.2 were likely imported from the region and confined to Sarawak state. Direct age-standardized seroprevalence in Kuala Lumpur/Selangor was 3.0%. The second and third waves were driven by super-spreading events and different circulating lineages. Malaysia is highly susceptible to further waves, especially as alpha (B.1.1.7) and beta (B.1.351) variants of concern were first detected in December 2020/January 2021. Increased genomic surveillance is critical.
  18. Sam IC, Karunakaran R, Kamarulzaman A, Ponnampalavanar S, Syed Omar SF, Ng KP, et al.
    J Hosp Infect, 2012 Apr;80(4):321-5.
    PMID: 22237130 DOI: 10.1016/j.jhin.2011.12.004
    Brucella species are easily transmitted by aerosols and can be acquired in the laboratory.
  19. Saeidi A, Chong YK, Yong YK, Tan HY, Barathan M, Rajarajeswaran J, et al.
    Cell Immunol, 2015 Sep;297(1):19-32.
    PMID: 26071876 DOI: 10.1016/j.cellimm.2015.05.005
    The role of T-cell immunosenescence and functional CD8(+) T-cell responses in HIV/TB co-infection is unclear. We examined and correlated surrogate markers of HIV disease progression with immune activation, immunosenescence and differentiation using T-cell pools of HIV/TB co-infected, HIV-infected and healthy controls. Our investigations showed increased plasma viremia and reduced CD4/CD8 T-cell ratio in HIV/TB co-infected subjects relative to HIV-infected, and also a closer association with changes in the expression of CD38, a cyclic ADP ribose hydrolase and CD57, which were consistently expressed on late-senescent CD8(+) T cells. Up-regulation of CD57 and CD38 were directly proportional to lack of co-stimulatory markers on CD8(+) T cells, besides diminished expression of CD127 (IL-7Rα) on CD57(+)CD4(+) T cells. Notably, intracellular IFN-γ, perforin and granzyme B levels in HIV-specific CD8(+) T cells of HIV/TB co-infected subjects were diminished. Intracellular CD57 levels in HIV gag p24-specific CD8(+) T cells were significantly increased in HIV/TB co-infection. We suggest that HIV-TB co-infection contributes to senescence associated with chronic immune activation, which could be due to functional insufficiency of CD8(+) T cells.
  20. Saeidi A, Tien Tien VL, Al-Batran R, Al-Darraji HA, Tan HY, Yong YK, et al.
    PLoS One, 2015;10(4):e0124659.
    PMID: 25894562 DOI: 10.1371/journal.pone.0124659
    Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved antimicrobial MR1-restricted CD8(+) T cells co-expressing the semi-invariant TCR Vα7.2, and are numerous in the blood and mucosal tissues of humans. MAIT cells appear to undergo exhaustion in chronic viral infections. However, their role in human immunodeficiency virus type 1 (HIV-1) mono-infection and HIV/tuberculosis (TB) co-infection have seldom been elaborately investigated. We conducted a cross-sectional study to investigate the frequencies and phenotypes of CD161(++)CD8(+) T cells among anti-retroviral therapy (ART)/anti-TB therapy (ATT) treatment-naïve HIV/TB co-infected, ART/TB treated HIV/TB co-infected, ART naïve HIV-infected, ART-treated HIV-infected patients, and HIV negative healthy controls (HCs) by flow cytometry. Our data revealed that the frequency of MAIT cells was severely depleted in HIV mono- and HIV/TB co-infections. Further, PD-1 expression on MAIT cells was significantly increased in HIV mono- and HIV-TB co-infected patients. The frequency of MAIT cells did not show any significant increase despite the initiation of ART and/or ATT. Majority of the MAIT cells in HCs showed a significant increase in CCR6 expression as compared to HIV/TB co-infections. No marked difference was seen with expressions of chemokine co-receptor CCR5 and CD103 among the study groups. Decrease of CCR6 expression appears to explain why HIV-infected patients display weakened mucosal immune responses.
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