Displaying publications 161 - 180 of 306 in total

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  1. Fulltext Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B) Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages
    Cheong HT, Chow WZ, Takebe Y, Chook JB, Chan KG, Al-Darraji HA, et al.
    PLoS One, 2015;10(7):e0133883.
    PMID: 26196131 DOI: 10.1371/journal.pone.0133883
    In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs). Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs), especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.
  2. Treatment of acute Nipah encephalitis with ribavirin
    Chong HT, Kamarulzaman A, Tan CT, Goh KJ, Thayaparan T, Kunjapan SR, et al.
    Ann Neurol, 2001 Jun;49(6):810-3.
    PMID: 11409437
    Nipah virus, a newly identified paramyxovirus caused a severe outbreak of encephalitis in Malaysia with high fatalities. We report an open-label trial of ribavirin in 140 patients, with 54 patients who were managed prior to the availability of ribavirin or refused treatment as control. There were 45 deaths (32%) in the ribavirin arm; 29 deaths (54%) occurred in the control arm. This represents a 36% reduction in mortality (p = 0.011). There was no associated serious side effect. This study suggests that ribavirin is able to reduce the mortality of acute Nipah encephalitis.
  3. Fatal encephalitis due to Nipah virus among pig-farmers in Malaysia
    Chua KB, Goh KJ, Wong KT, Kamarulzaman A, Tan PS, Ksiazek TG, et al.
    Lancet, 1999 Oct 9;354(9186):1257-9.
    PMID: 10520635
    Between February and April, 1999, an outbreak of viral encephalitis occurred among pig-farmers in Malaysia. We report findings for the first three patients who died.
  4. High mortality in Nipah encephalitis is associated with presence of virus in cerebrospinal fluid
    Chua KB, Lam SK, Tan CT, Hooi PS, Goh KJ, Chew NK, et al.
    Ann Neurol, 2000 Nov;48(5):802-5.
    PMID: 11079547
    During the outbreak of Nipah virus encephalitis in Malaysia, stored cerebrospinal fluid (CSF) samples from 84 patients (27 fatal and 57 nonfatal cases) were cultured for the virus. The virus was isolated from 17 fatal cases and 1 nonfatal case. There were significant associations between CSF virus isolation and mortality as well as clinical features associated with poor prognosis. In addition, there was a positive linear correlation of CSF virus isolation with age. There was no significant association between CSF virus isolation and the character of the CSF, presence of Nipah-specific antibody in the serum or CSF, duration of illness before collection of samples, or sex or ethnicity of the patients. This study suggests that high viral replication in the central nervous system may be an important factor for high mortality.
  5. Risk Factors for a Positive Hepatitis C Status in Fishermen in Kuantan Malaysia
    Lall P, Saifi R, Baggio D, Schoenberger SF, Choo M, Gilbert L, et al.
    Asia Pac J Public Health, 2019 04;31(3):227-237.
    PMID: 30983376 DOI: 10.1177/1010539519841294
    Malaysia currently has an estimated hepatitis C virus (HCV) prevalence of 1.3% with an infected population of 384,000. Fishermen in Malaysia are at risk of HCV infection due to injection drug use and disproportionately high rates of incarceration. This study used quantitative data from Project WAVES, a large-scale mixed methods project charting environmental drivers of risk-taking behaviors among a respondent-driven sample of 406 fishermen in Malaysia. Over a quarter of participants (27.9%) reported injecting drugs in the past month; 49.8% of the sample tested positive for HCV. Respondents who had previously been arrested displayed increased odds of being HCV-positive (adjusted odds ratio = 4.79, confidence Interval = 2.46-9.35). Participants who reported being in lock-up displayed close to 6-fold odds of being HCV-infected (adjusted odds ratio = 5.49, confidence interval = 2.77-10.90, P < .001). These findings underscore the need for policies and structural interventions targeting the negative effects of aggressive incarceration contributing to the burden of HCV among high-risk communities.
  6. Fulltext Use of Smartphone to Seek Sexual Health Information Online Among Malaysian Men Who Have Sex with Men (MSM): Implications for mHealth Intervention to Increase HIV Testing and Reduce HIV Risks
    Shrestha R, Lim SH, Altice FL, Copenhaver M, Wickersham JA, Saifi R, et al.
    J Community Health, 2020 02;45(1):10-19.
    PMID: 31375976 DOI: 10.1007/s10900-019-00713-x
    In settings where stigma and discrimination toward men who have sex with men (MSM) are high or illegal, like in Malaysia, innovative methods to anonymously reach them are urgently needed. The near ubiquitous availability of mobile technology, including smartphones, has the potential to open new frontiers (such as mHealth) to prevent HIV and other sexually transmitted infections (STIs). The extent to which MSM use mHealth tools for HIV and STI prevention in the Malaysia context, however, is unknown. A cross-sectional online survey in 622 Malaysian MSM was conducted between July and November 2017. Participants were recruited via advertisements on mobile apps frequently used by MSM. In addition to demographic, smartphone access and utilization, and other information were assessed using logistic regression to determine factors associated with the use of a smartphone to search for online sexual health information. Nearly all (99.2%) participants owned a smartphone, with 63% reported having used one to seek sexual health information, including HIV/STIs. Overall, 96% used smartphones to find sexual partners, with high levels of HIV risk behavior reported. Independent correlates of smartphone use to seek online sexual health information included older age (aOR 0.943, p = 0.005), higher education (aOR 2.14, p = 027), recent (past year) HIV testing (aOR 3.91, p = 0.026), and seeking sexual partners using geosocial networking apps (aOR 5.58, p = 0.006). These findings suggest high smartphone use by high-risk MSM to seek sexual health information and suggests that mHealth strategies may be an effective strategy to engage MSM in HIV prevention activities.
  7. Fulltext An exploratory qualitative assessment of self-reported treatment outcomes and satisfaction among patients accessing an innovative voluntary drug treatment centre in Malaysia
    Ghani MA, Brown SE, Khan F, Wickersham JA, Lim SH, Dhaliwal SK, et al.
    Int J Drug Policy, 2015 Feb;26(2):175-82.
    PMID: 25577322 DOI: 10.1016/j.drugpo.2014.10.002
    BACKGROUND: In Malaysia, compulsory drug detention centres (CDDCs) hold suspected drug users for two years without adjudication. Acute detoxification without healthcare access has been documented. CDDCs are criticized globally due to ineffectiveness in treating addiction and human rights violations. In response, the Malaysian government began transitioning these facilities into voluntary drug treatment centres known as "Cure and Care" (C&C) centres that embrace a holistic treatment-based approach to drug addiction rehabilitation.

    METHODS: An explorative qualitative study was undertaken to explore patient perspectives and satisfaction regarding treatment and services at the new Cure and Care centre in Kota Bharu, Malaysia. A convenience sample of 20 patients was recruited to participate in semi-structured in-depth interviews. Content analysis was used to identify the salient themes.

    RESULTS: Patients identified methadone treatment, psychosocial programs, religious instruction, and recreational activities as important factors contributing to treatment success for addressing both health and addiction needs. Though many had previously been in a CDDC, adherence to treatment in the C&C centre was perceived to be facilitated by the degree of social support, the voluntary nature and the array of new programs available for selection.

    CONCLUSION: C&Cs represents a dramatic shift in the Malaysian government's approach to drug addiction. Our findings demonstrate positive patient experiences associated with the holistic treatment-based approach of these centres. This exploratory study provides additional evidence to document this ongoing policy transition and may guide continued expansion of new holistic drug treatment programs across the country.

  8. What has been achieved in HIV prevention, treatment and care for people who inject drugs, 2010-2012? A review of the six highest burden countries
    Degenhardt L, Mathers BM, Wirtz AL, Wolfe D, Kamarulzaman A, Carrieri MP, et al.
    Int J Drug Policy, 2014 Jan;25(1):53-60.
    PMID: 24113623 DOI: 10.1016/j.drugpo.2013.08.004
    In 2010 the international HIV/AIDS community called on countries to take action to prevent HIV transmission among people who inject drugs (PWID). To set a baseline we proposed an "accountability matrix", focusing upon six countries accounting for half of the global population of PWID: China, Malaysia, Russia, Ukraine, Vietnam and the USA. Two years on, we review progress.
  9. Tuberculosis screening in a novel substance abuse treatment center in Malaysia: implications for a comprehensive approach for integrated care
    Al-Darraji HA, Wong KC, Yeow DG, Fu JJ, Loeliger K, Paiji C, et al.
    J Subst Abuse Treat, 2014 Feb;46(2):144-9.
    PMID: 24074846 DOI: 10.1016/j.jsat.2013.08.023
    People who use drugs (PWUD) represent a key high risk group for tuberculosis (TB). The prevalence of both latent TB infection (LTBI) and active disease in drug treatment centers in Malaysia is unknown. A cross-sectional convenience survey was conducted to assess the prevalence and correlates of LTBI among attendees at a recently created voluntary drug treatment center using a standardized questionnaire and tuberculin skin testing (TST). Participants (N=196) were mostly men (95%), under 40 (median age=36 years) and reported heroin use immediately before treatment entry (75%). Positive TST prevalence was 86.7%. Nine (4.6%) participants were HIV-infected. Previous arrest/incarcerations (AOR=1.1 for every entry, p<0.05) and not being HIV-infected (AOR=6.04, p=0.03) were significantly associated with TST positivity. There is an urgent need to establish TB screening and treatment programs in substance abuse treatment centers and to tailor service delivery to the complex treatment needs of patients with multiple medical and psychiatric co-morbidities.
  10. Fulltext Aberrant Inflammasome Activation Characterizes Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome
    Tan HY, Yong YK, Shankar EM, Paukovics G, Ellegård R, Larsson M, et al.
    J Immunol, 2016 05 15;196(10):4052-63.
    PMID: 27076678 DOI: 10.4049/jimmunol.1502203
    Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) complicates combination antiretroviral therapy (cART) in up to 25% of patients with HIV/TB coinfection. Monocytes and IL-18, a signature cytokine of inflammasome activation, are implicated in TB-IRIS pathogenesis. In this study, we investigated inflammasome activation both pre- and post-cART in TB-IRIS patients. HIV/TB patients exhibited higher proportions of monocytes expressing activated caspase-1 (casp1) pre-cART, compared with HIV patients without TB, and patients who developed TB-IRIS exhibited the greatest increase in casp1 expression. CD64(+) monocytes were a marker of increased casp1 expression. Furthermore, IL-1β, another marker of inflammasome activation, was also elevated during TB-IRIS. TB-IRIS patients also exhibited greater upregulation of NLRP3 and AIM2 inflammasome mRNA, compared with controls. Analysis of plasma mitochondrial DNA levels showed that TB-IRIS patients experienced greater cell death, especially pre-cART. Plasma NO levels were lower both pre- and post-cART in TB-IRIS patients, providing evidence of inadequate inflammasome regulation. Plasma IL-18 levels pre-cART correlated inversely with NO levels but positively with monocyte casp1 expression and mitochondrial DNA levels, and expression of IL-18Rα on CD4(+) T cells and NK cells was higher in TB-IRIS patients, providing evidence that IL-18 is a marker of inflammasome activation. We propose that inflammasome activation in monocytes/macrophages of HIV/TB patients increases with ineffective T cell-dependent activation of monocytes/macrophages, priming them for an excessive inflammatory response after cART is commenced, which is greatest in patients with TB-IRIS.
  11. Fulltext HIV care models during the COVID-19 era
    Guaraldi G, Milic J, Martinez E, Kamarulzaman A, Mussini C, Waters L, et al.
    Clin Infect Dis, 2020 Dec 19.
    PMID: 33340037 DOI: 10.1093/cid/ciaa1864
    The COVID-19 pandemic is an unprecedented global challenge that substantially risks reversing the progress in ending HIV. At the same time, it may offer the opportunity for a new era of HIV management. This viewpoint presents the impact of COVID-19 on HIV care, including the Joint United Nations Programme on HIV/AIDS (UNAIDS) "three 90s" targets. It outlines how to enhance a patient-centered care approach, now known as the "fourth 90," by integrating face-to-face patient-physician and telemedicine encounters. It suggests a framework for prevention and treatment of multimorbidity and frailty, to achieve a good health-related quality of life and preserve intrinsic capacity in all people living with HIV.
  12. Correlates of newly diagnosed HIV infection among cisgender women sex workers and transgender women sex workers in Greater Kuala Lumpur, Malaysia
    Wang M, Lim SH, Gibson BA, Azwa I, Guadamuz TE, Altice FL, et al.
    Int J STD AIDS, 2021 06;32(7):609-619.
    PMID: 33752518 DOI: 10.1177/0956462420970417
    Globally, cisgender women sex workers (CWSWs) and transgender women sex workers (TWSWs) experience increased vulnerabilities to HIV infection. Unfortunately, there is limited data on the drivers of HIV infection in these two understudied populations, particularly in Southeast Asia. To better understand factors associated with HIV infection, we evaluated correlates of newly diagnosed HIV infection in these two populations in Greater Kuala Lumpur, Malaysia. A total of 469 women (CWSW: n = 283; TWSW: n = 186) were included in this study. Most participants who tested HIV+ were unaware of their infection (59.6%; n = 34/57). Separate binary and multivariable logistic regressions were conducted to identify correlates of newly diagnosed HIV in CWSWs and TWSWs. Among CWSWs, Chlamydia trachomatis (aOR = 5.66; p = 0.007) and lifetime use of ecstasy/MDMA (aOR = 5.34; p = 0.03) were associated with newly diagnosed HIV, while condomless vaginal sex with clients was associated with lower likelihood of HIV infection (aOR = 0.98; p = 0.01). Among TWSWs, being single (aOR = 6.76; p = 0.03), using mobile application to solicit clients (aOR = 25.33; p = 0.006), and having C. trachomatis infection (aOR = 88.22, p = 0.02) were associated with newly diagnosed HIV. Expansion of HIV/sexually transmitted infection screening is needed to increase detection of HIV and linkage to care for sex workers. Interventions to reduce HIV infection among CWSWs and TWSWs should be tailored to these populations' unique vulnerabilities.
  13. Prevention of transmission of HIV, hepatitis B virus, hepatitis C virus, and tuberculosis in prisoners
    Kamarulzaman A, Reid SE, Schwitters A, Wiessing L, El-Bassel N, Dolan K, et al.
    Lancet, 2016 Sep 10;388(10049):1115-1126.
    PMID: 27427456 DOI: 10.1016/S0140-6736(16)30769-3
    The prevalence of HIV, hepatitis B virus, hepatitis C virus, and tuberculosis are higher in prisons than in the general population in most countries worldwide. Prisons have emerged as a risk environment for these infections to be further concentrated, amplified, and then transmitted to the community after prisoners are released. In the absence of alternatives to incarceration, prisons and detention facilities could be leveraged to promote primary and secondary prevention strategies for these infections to improve prisoners health and reduce risk throughout incarceration and on release. Effective treatment of opioid use disorders with opioid agonist therapies (eg, methadone and buprenorphine) prevents blood-borne infections via reductions in injection in prison and after release. However, large gaps exist in the implementation of these strategies across all regions. Collaboration between the criminal justice and public health systems will be required for successful implementation of these strategies.
  14. Fulltext Genetic polymorphisms in the CD14 gene are associated with monocyte activation and carotid intima-media thickness in HIV-infected patients on antiretroviral therapy
    Yong YK, Shankar EM, Westhorpe CL, Maisa A, Spelman T, Kamarulzaman A, et al.
    Medicine (Baltimore), 2016 Aug;95(31):e4477.
    PMID: 27495090 DOI: 10.1097/MD.0000000000004477
    HIV-infected individuals on antiretroviral therapy (ART) are at increased risk of cardiovascular disease (CVD). Given the relationship between innate immune activation and CVD, we investigated the association of single-nucleotide polymorphisms (SNPs) in TLR4 and CD14 and carotid intima-media thickness (cIMT), a surrogate measurement for CVD, in HIV-infected individuals on ART and HIV-uninfected controls as a cross-sectional, case-control study. We quantified the frequency of monocyte subsets (CD14, CD16), markers of monocyte activation (CD38, HLA-DR), and endothelial adhesion (CCR2, CX3CR1, CD11b) by flow cytometry. Plasma levels of lipopolysaccharide, sCD163, sCD14, sCX3CL1, and sCCL2, were measured by ELISA. Genotyping of TLR4 and CD14 SNPs was also performed. The TT genotype for CD14/-260SNP but not the CC/CT genotype was associated with elevated plasma sCD14, and increased frequency of CD11b+CD14+ monocytes in HIV-infected individuals. The TT genotype was associated with lower cIMT in HIV-infected patients (n = 47) but not in HIV-uninfected controls (n = 37). The AG genotype for TLR4/+896 was associated with increased CX3CR1 expression on total monocytes among HIV-infected individuals and increased sCCL2 and fibrinogen levels in HIV-uninfected controls. SNPs in CD14/-260 and TLR4/+896 were significantly associated with different markers of systemic and monocyte activation and cIMT that differed between HIV-infected participants on ART and HIV-uninfected controls. Further investigation on the relationship of these SNPs with a clinical endpoint of CVD is warranted in HIV-infected patients on ART.
  15. Human papillomavirus 16 (HPV16) and HPV52 E6-specific immunity in HIV-infected adults on combination antiretroviral therapy
    Leng CY, Low HC, Chua LL, Chong ML, Sulaiman H, Azwa I, et al.
    HIV Med, 2017 05;18(5):321-331.
    PMID: 27649852 DOI: 10.1111/hiv.12432
    OBJECTIVES: Human papillomavirus (HPV)-associated cancers disproportionately affect those infected with HIV despite effective combination antiretroviral therapy (cART). The primary aim of this study was to quantify HPV16 and HPV52 E6-specific interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) T-cell responses, a correlate of protective immunity, in the first year following cART initiation and subsequently in those patients with suboptimal (sIR) and optimal (oIR) immune reconstitution.

    METHODS: Ninety-four HIV-infected patients were recruited to the study; a longitudinal cohort of patients recruited just prior to commencing cART and followed up for 48 weeks (n = 27), and a cross-sectional cohort (n = 67) consisting of patients with sIR (CD4 T-cell count < 350 cells/μL) and oIR (CD4 T-cell count > 500 cells/μL) after a minimum of 2 years on cART. Controls (n = 29) consisted of HIV-negative individuals. IFN-γ ELISPOT responses against HPV16 and HPV52 E6 were correlated to clinical characteristics, anal and oral HPV carriage, T-cell maturational subsets, markers of activation, senescence and T-regulatory cells.

    RESULTS: HPV16 and HPV52 E6-specific T-cell responses were detected in only one of 27 patients (3.7%) during the initial phase of immune recovery. After at least 2 years of cART, those who achieved oIR had significantly higher E6-specific responses (9 of 34; 26.5%) compared with those with sIR (2 of 32; 6.3%) (P = 0.029). Apart from higher CD4 T-cell counts and lower CD4 T-cell activation, no other immunological correlates were associated with the detection of HPV16 and HPV52 E6-specific responses.

    CONCLUSIONS: HPV16 and HPV52 E6-specific IFN-γ T-cell responses, a correlate of protective immunity, were detected more frequently among HIV-infected patients who achieved optimal immune recovery on cART (26.5%) compared with those with suboptimal recovery (6.3%).

  16. Fulltext Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection and the molecular characteristics of MRSA bacteraemia over a two-year period in a tertiary teaching hospital in Malaysia
    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 

  17. Identification and evolutionary dynamics of two novel human coronavirus OC43 genotypes associated with acute respiratory infections: phylogenetic, spatiotemporal and transmission network analyses
    Oong XY, Ng KT, Takebe Y, Ng LJ, Chan KG, Chook JB, et al.
    Emerg Microbes Infect, 2017 Jan 04;6(1):e3.
    PMID: 28050020 DOI: 10.1038/emi.2016.132
    Human coronavirus OC43 (HCoV-OC43) is commonly associated with respiratory tract infections in humans, with five genetically distinct genotypes (A to E) described so far. In this study, we obtained the full-length genomes of HCoV-OC43 strains from two previously unrecognized lineages identified among patients presenting with severe upper respiratory tract symptoms in a cross-sectional molecular surveillance study in Kuala Lumpur, Malaysia, between 2012 and 2013. Phylogenetic, recombination and comparative genomic analyses revealed two distinct clusters diverging from a genotype D-like common ancestor through recombination with a putative genotype A-like lineage in the non-structural protein (nsp) 10 gene. Signature amino acid substitutions and a glycine residue insertion at the N-terminal domain of the S1 subunit of the spike gene, among others, exhibited further distinction in a recombination pattern, to which these clusters were classified as genotypes F and G. The phylogeographic mapping of the global spike gene indicated that the genetically similar HCoV-OC43 genotypes F and G strains were potentially circulating in China, Japan, Thailand and Europe as early as the late 2000s. The transmission network construction based on the TN93 pairwise genetic distance revealed the emergence and persistence of multiple sub-epidemic clusters of the highly prevalent genotype D and its descendant genotypes F and G, which contributed to the spread of HCoV-OC43 in the region. Finally, a more consistent nomenclature system for non-recombinant and recombinant HCoV-OC43 lineages is proposed, taking into account genetic recombination as an important feature in HCoV evolution and classification.
  18. Fulltext Negative Checkpoint Regulatory Molecule 2B4 (CD244) Upregulation Is Associated with Invariant Natural Killer T Cell Alterations and Human Immunodeficiency Virus Disease Progression
    Ahmad F, Shankar EM, Yong YK, Tan HY, Ahrenstorf G, Jacobs R, et al.
    Front Immunol, 2017;8:338.
    PMID: 28396665 DOI: 10.3389/fimmu.2017.00338
    The CD1d-restricted invariant natural killer T (iNKT) cells are implicated in innate immune responses against human immunodeficiency virus (HIV). However, the determinants of cellular dysfunction across the iNKT cells subsets are seldom defined in HIV disease. Herein, we provide evidence for the involvement of the negative checkpoint regulator (NCR) 2B4 in iNKT cell alteration in a well-defined cohort of HIV-seropositive anti-retroviral therapy (ART) naïve, ART-treated, and elite controllers (ECs). We report on exaggerated 2B4 expression on iNKT cells of HIV-infected treatment-naïve individuals. In sharp contrast to CD4(-)iNKT cells, 2B4 expression was significantly higher on CD4(+) iNKT cell subset. Notably, an increased level of 2B4 on iNKT cells was strongly correlated with parameters associated with HIV disease progression. Further, iNKT cells from ART-naïve individuals were defective in their ability to produce intracellular IFN-γ. Together, our results suggest that the levels of 2B4 expression and the downstream co-inhibitory signaling events may contribute to impaired iNKT cell responses.
  19. Fulltext Assessment of an innovative voluntary substance abuse treatment program designed to replace compulsory drug detention centers in Malaysia
    Khan F, Krishnan A, Ghani MA, Wickersham JA, Fu JJ, Lim SH, et al.
    Subst Use Misuse, 2018 01 28;53(2):249-259.
    PMID: 28635521 DOI: 10.1080/10826084.2016.1267217
    BACKGROUND: As part of an ongoing initiative by the Malaysian government to implement alternative approaches to involuntary detention of people who use drugs, the National Anti-Drug Agency has created new voluntary drug treatment programs known as Cure and Care (C&C) Centers that provide free access to addiction treatment services, including methadone maintenance therapy, integrated with social and health services.

    OBJECTIVES: We evaluated early treatment outcomes and client satisfaction among patients accessing C&C treatment and ancillary services at Malaysia's second C&C Center located in Kota Bharu, Kelantan.

    METHODS: In June-July 2012, a cross-sectional convenience survey of 96 C&C inpatients and outpatients who entered treatment >30 days previously was conducted to assess drug use, criminal justice experience, medical co-morbidities, motivation for seeking treatment, and attitudes towards the C&C. Drug use was compared for the 30-day-period before C&C entry and the 30-day-period before the interview.

    RESULTS: Self-reported drug use levels decreased significantly among both inpatient and outpatient clients after enrolling in C&C treatment. Higher levels of past drug use, lower levels of social support, and more severe mental health issues were reported by participants who were previously imprisoned. Self-reported satisfaction with C&C treatment services was high. Conclusions/Importance: Preliminary evidence of reduced drug use and high levels of client satisfaction among C&C clients provide support for Malaysia's ongoing transition from compulsory drug detention centers (CDDCs) to these voluntary drug treatment centers. If C&C centers are successful, Malaysia plans to gradually transition away from CDDCs entirely.
  20. Fulltext Performance of a Taqman Assay for Improved Detection and Quantification of Human Rhinovirus Viral Load
    Ng KT, Chook JB, Oong XY, Chan YF, Chan KG, Hanafi NS, et al.
    Sci Rep, 2016 10 10;6:34855.
    PMID: 27721388 DOI: 10.1038/srep34855
    Human rhinovirus (HRV) is the major aetiology of respiratory tract infections. HRV viral load assays are available but limitations that affect accurate quantification exist. We developed a one-step Taqman assay using oligonucleotides designed based on a comprehensive list of global HRV sequences. The new oligonucleotides targeting the 5'-UTR region showed high PCR efficiency (E = 99.6%, R2 = 0.996), with quantifiable viral load as low as 2 viral copies/μl. Assay evaluation using an External Quality Assessment (EQA) panel yielded a detection rate of 90%. When tested on 315 human enterovirus-positive specimens comprising at least 84 genetically distinct HRV types/serotypes (determined by the VP4/VP2 gene phylogenetic analysis), the assay detected all HRV species and types, as well as other non-polio enteroviruses. A commercial quantification kit, which failed to detect any of the EQA specimens, produced a detection rate of 13.3% (42/315) among the clinical specimens. Using the improved assay, we showed that HRV sheds in the upper respiratory tract for more than a week following acute infection. We also showed that HRV-C had a significantly higher viral load at 2-7 days after the onset of symptoms (p = 0.001). The availability of such assay is important to facilitate disease management, antiviral development, and infection control.
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