Displaying publications 61 - 80 of 307 in total

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  1. Ng KT, Takebe Y, Kamarulzaman A, Tee KK
    Arch Virol, 2021 Jan;166(1):225-229.
    PMID: 33084935 DOI: 10.1007/s00705-020-04855-5
    Genome sequences of members of a potential fourth rhinovirus (RV) species, provisionally denoted as rhinovirus A clade D, from patients with acute respiratory infection were determined. Bayesian coalescent analysis estimated that clade D emerged around the 1940s and diverged further around 2006-2007 into two distinctive sublineages (RV-A8-like and RV-A45-like) that harbored unique "clade-defining" substitutions. Similarity plots and bootscan mapping revealed a recombination breakpoint located in the 5'-UTR region of members of the RV-A8-like sublineage. Phylogenetic reconstruction revealed the distribution of clade D viruses in the Asia Pacific region and in Europe, underlining its worldwide distribution.
  2. Krishna S, Augustin Y, Wang J, Xu C, Staines HM, Platteeuw H, et al.
    Trends Parasitol, 2021 01;37(1):8-11.
    PMID: 33153922 DOI: 10.1016/j.pt.2020.10.003
    Artemisinin-based combination therapies (ACTs) have demonstrated in vitro inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Artemisinins have also shown anti-inflammatory effects, including inhibition of interleukin-6 (IL-6) that plays a key role in the development of severe coronavirus disease 2019 (COVID-19). There is now sufficient evidence for the effectiveness of ACTs, and in particular artesunate/pyronaridine, to support clinical studies for COVID-19 infections.
  3. Vicknasingam B, Mohd Salleh NA, Chooi WT, Singh D, Mohd Zaharim N, Kamarulzaman A, et al.
    Front Psychiatry, 2021;12:630730.
    PMID: 33854449 DOI: 10.3389/fpsyt.2021.630730
    Background: Restrictive orders and temporary programmatic or ad hoc changes within healthcare and other supportive systems that were implemented in response to the COVID-19 epidemic in Malaysia may have created hindrances to accessing healthcare and/or receiving other supportive services for people who use drugs (PWUDs). Design: A primarily qualitative study has been conducted to evaluate how service providers and recipients were adapting and coping during the initial periods of the COVID-19 response. Settings: The study engaged several healthcare and non-governmental organizations (NGOs) in the peninsular states of Penang, Kelantan, Selangor, and Melaka. Participants: Medical personnel of methadone maintenance treatment (MMT) programs (n = 2) and HIV clinics (n = 3), staff of NGO services (n = 4), and MMT patients (n = 9) were interviewed using a semi-structured format. Results: Interviewed participants reported significant organizational, programmatic, and treatment protocols related changes implemented within the healthcare and support services in addition to nationally imposed Movement Control Orders (MCOs). Changes aimed to reduce patient flow and concentration at the on-site services locations, including less frequent in-person visits, increased use of telemedicine resources, and greater reliance on telecommunication methods to maintain contacts with patients and clients; changes in medication dispensing protocols, including increased take-home doses and relaxed rules for obtaining them, or delivery of medications to patients' homes or locations near their homes were reported by the majority of study participants. No significant rates of COVID-19 infections among PWUDs, including among those with HIV have been reported at the study sites. Conclusions: Although the reported changes presented new challenges for both services providers and recipients and resulted in some degree of initial disruption, generally, all participants reported successful implementation and high levels of compliance with the newly introduced restrictions, regulations, and protocols, resulting in relatively low rates of treatment disruption or discontinuation at the study sites.
  4. 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.

  5. Krishnan A, Weikum D, Cravero C, Kamarulzaman A, Altice FL
    PLoS One, 2021;16(3):e0248705.
    PMID: 33755693 DOI: 10.1371/journal.pone.0248705
    BACKGROUND: Mobile health (mHealth) can be beneficial in monitoring the complex healthcare regimen for people with HIV that includes adhering to medication and refraining from risky practices such as unsafe sex and injection drug use. Not only is mHealth often implemented without appropriate feasibility and acceptability research, but there is limited mHealth research among key HIV-positive populations such as men who have sex with men (MSM) and transgender women (TGW).

    METHODS: This study assessed access to and use of mobile technology and acceptability of mHealth among 150 HIV-positive MSM and TGW who were prescribed antiretroviral therapy (ART) in Malaysia-an emerging economy with rapid telecommunications growth and societal stigma against these groups.

    RESULTS: Findings among the 114 MSM and 36 TGW reveal high levels of depression (42%), stigma (2.53/4.00) and risky sexual behavior (30%), and suboptimal ART adherence (22%). On the other hand, the sample had excellent access to smartphones (75.3%) and the internet (78%), and had high acceptance of mHealth especially for those with suboptimal ART adherence.

    CONCLUSION: In settings like Malaysia where homosexuality and cross-dressing are socially and legally stigmatized, HIV prevention and treatment strategies delivered using an mHealth platform have the potential to overcome in-person barriers.

  6. 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.
  7. Chong YM, Sam IC, Chong J, Kahar Bador M, Ponnampalavanar S, Syed Omar SF, et al.
    PLoS Negl Trop Dis, 2020 11;14(11):e0008744.
    PMID: 33253226 DOI: 10.1371/journal.pntd.0008744
    Malaysia had 10,219 confirmed cases of COVID-19 as of September 20, 2020. About 33% were associated with a Tablighi Jamaat religious mass gathering held in Kuala Lumpur between February 27 and March 3, 2020, which drove community transmission during Malaysia's second wave. We analysed genome sequences of SARS-CoV-2 from Malaysia to better understand the molecular epidemiology and spread. We obtained 58 SARS-CoV-2 whole genome sequences from patients in Kuala Lumpur and performed phylogenetic analyses on these and a further 57 Malaysian sequences available in the GISAID database. Nine different SARS-CoV-2 lineages (A, B, B.1, B.1.1, B.1.1.1, B.1.36, B.2, B.3 and B.6) were detected in Malaysia. The B.6 lineage was first reported a week after the Tablighi mass gathering and became predominant (65.2%) despite being relatively rare (1.4%) globally. Direct epidemiological links between lineage B.6 viruses and the mass gathering were identified. Increases in reported total cases, Tablighi-associated cases, and community-acquired B.6 lineage strains were temporally linked. Non-B.6 lineages were mainly travel-associated and showed limited onward transmission. There were also temporally correlated increases in B.6 sequences in other Southeast Asian countries, India and Australia, linked to participants returning from this event. Over 95% of global B.6 sequences originated from Asia Pacific. We also report a nsp3-C6310A substitution found in 47.3% of global B.6 sequences which was associated with reduced sensitivity using a commercial diagnostic real-time PCR assay. Lineage B.6 became the predominant cause of community transmission in Malaysia after likely introduction during a religious mass gathering. This event also contributed to spikes of lineage B.6 in other countries in the Asia-Pacific. Mass gatherings can be significant causes of local and global spread of COVID-19. Shared genomic surveillance can be used to identify SARS-CoV-2 transmission chains to aid prevention and control, and to monitor diagnostic molecular assays. Clinical Trial Registration: COVID-19 paper.
  8. Meng Li C, Jie Ying F, Raj D, Pui Li W, Kukreja A, Omar SF, et al.
    J Int AIDS Soc, 2020 Nov;23(11):e25638.
    PMID: 33206473 DOI: 10.1002/jia2.25638
    INTRODUCTION: The rapidly growing epidemic of non-communicable diseases (NCDs) including mental health among aging people living with HIV (PLWH) has put a significant strain on the provision of health services in many HIV clinics globally. We constructed care cascades for specific NCDs and mental health among PLWH attending our centre to identify potential areas for programmatic improvement.

    METHODS: This was a follow-up study of participants recruited in the Malaysian HIV & Aging study (MHIVA) from 2014 to 2016 at the University Malaya Medical Centre (n = 336). PLWH on suppressive antiretroviral therapy (ART) for a minimum of 12 months were invited to participate. At study entry, all participants underwent screening for diabetes (DM), hypertension (HTN) and dyslipidaemia; and completed assessments using the depression, anxiety and stress scale (DASS-21). Screening results were recorded in medical charts and clinical management provided as per standard of care. A subsequent review of medical records was performed at 24 months following study completion among participants who remained on active follow-up. Treatment pathways for NCD treatment and psychiatric referrals were assessed based on local practice guidelines to construct the care cascade.

    RESULTS: A total of 329 participants (median age = 43 years, 83% male, 100% on ART) completed follow-up at 24 months. The prevalence of diabetes was 13%, dyslipidaemia 88% and hypertension 44%, whereas 23% presented with severe/extremely severe symptoms of depression, anxiety and/or stress. More than 50% of participants with dyslipidaemia and hypertension were not diagnosed until study screening, whereas over 80% with prevalent psychiatric symptoms were not previously recognized clinically. Suboptimal control of fasting lipids, sugar and blood pressure were found in the majority of participants despite optimal HIV treatment outcomes maintained over this same period. Only 32% of participants with severe/extremely severe mental health symptoms received psychiatric referrals and 83% of these attended their psychiatry clinic appointments.

    CONCLUSIONS: Systematic screening must be introduced to identify NCDs and mental health issues among PLWH followed by proper linkage and referrals for management of screen-positive cases. Assessment of factors associated with attrition at each step of the care cascade is critically needed to improve health outcomes in our aging patients.

  9. McMahon JH, Hoy JF, Kamarulzaman A, Bekker LG, Beyrer C, Lewin SR
    Lancet, 2020 10 03;396(10256):943-944.
    PMID: 33010825 DOI: 10.1016/S0140-6736(20)32012-2
  10. Panickar R, Wo WK, Ali NM, Tang MM, Ramanathan GRL, Kamarulzaman A, et al.
    Pharmacoepidemiol Drug Saf, 2020 10;29(10):1254-1262.
    PMID: 33084196 DOI: 10.1002/pds.5033
    PURPOSE: To describe risk minimization measures (RMMs) implemented in Malaysia for allopurinol-induced severe cutaneous adverse drug reactions (SCARs) and examine their impact using real-world data on allopurinol usage and adverse drug reaction (ADR) reports associated with allopurinol.

    METHODS: Data on allopurinol ADR reports (2000-2018) were extracted from the Malaysian ADR database. We identified RMMs implemented between 2000 and 2018 from the minutes of relevant meetings and the national pharmacovigilance newsletter. We obtained allopurinol utilization data (2004-2018) from the Pharmaceutical Services Programme. To determine the impact of RMMs on ADR reporting, we considered ADR reports received within 1 year of RMM implementation. We used the Pearson χ2 test to examine the relation between the implementation of RMMs and allopurinol ADR reports.

    RESULTS: The 16 RMMs for allopurinol-related SCARs implemented in Malaysia involved nine risk communications, four prescriber or patient educational material, and three health system innovations. Allopurinol utilization decreased by 21.5% from 2004 to 2018. ADR reporting rates for all drugs (n = 144 507) and allopurinol (n = 1747) increased. ADR reports involving off-label use decreased by 6% from 2011. SCARs cases remained between 20% and 50%. RMMs implemented showed statistically significant reduction in ADR reports involving off-label use for August 2014 [χ2(1, N = 258) = 5.32, P = .021] and October 2016 [χ2(1, N = 349) = 3.85, P = .0499].

    CONCLUSIONS: RMMs to promote the appropriate use of allopurinol and prescriber education have a positive impact. We need further measures to reduce the incidence and severity of allopurinol-induced SCARs, such as patient education and more research into pharmacogenetic screening.

  11. Yap PSX, Tan TS, Chan YF, Tee KK, Kamarulzaman A, Teh CSJ
    J Microbiol Biotechnol, 2020 Jul 28;30(7):962-966.
    PMID: 32627759 DOI: 10.4014/jmb.2006.06009
    Monitoring the mutation dynamics of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical in understanding its infectivity, virulence and pathogenicity for development of a vaccine. In an "age of mobility," the pandemic highlights the importance and vulnerability of regionalization and labor market interdependence in Southeast Asia. We intend to characterize the genetic variability of viral populations within the region to provide preliminary information for regional surveillance in the future. By analyzing 142 complete genomes from South East Asian (SEA) countries, we identified three central variants distinguished by nucleotide and amino acid changes.
  12. Archuleta S, Chia PY, Wei Y, Syed-Omar SF, Low JG, Oh HM, et al.
    Clin Infect Dis, 2020 07 11;71(2):383-389.
    PMID: 31626692 DOI: 10.1093/cid/ciz850
    BACKGROUND: Platelet transfusion is common in dengue patients with thrombocytopenia. We previously showed in a randomized clinical trial that prophylactic platelet transfusion did not reduce clinical bleeding. In this study, we aimed to characterize the predictors and clinical outcomes of poor platelet recovery in transfused and nontransfused participants.

    METHODS: We analyzed patients from the Adult Dengue Platelet Study with laboratory-confirmed dengue with ≤20 000 platelets/μL and without persistent mild bleeding or any severe bleeding in a post hoc analysis. Poor platelet recovery was defined as a platelet count of ≤20 000/μL on Day 2. We recruited 372 participants from 5 acute care hospitals located in Singapore and Malaysia between 29 April 2010 and 9 December 2014. Of these, 188 were randomly assigned to the transfusion group and 184 to the control group.

    RESULTS: Of 360 patients, 158 had poor platelet recovery. Age, white cell count, and day of illness at study enrollment were significant predictors of poor platelet recovery after adjustment for baseline characteristics and platelet transfusion. Patients with poor platelet recovery had longer hospitalizations but no significant difference in other clinical outcomes, regardless of transfusion. We found a significant interaction between platelet recovery and transfusion; patients with poor platelet recovery were more likely to bleed if given a prophylactic platelet transfusion (odds ratio 2.34, 95% confidence interval 1.18-4.63).

    CONCLUSIONS: Dengue patients with thrombocytopenia who were older or presented earlier and with lower white cell counts were more likely to have poor platelet recovery. In patients with poor platelet recovery, platelet transfusion does not improve outcomes and may actually increase the risk of bleeding. The mechanisms of poor platelet recovery need to be determined.

    CLINICAL TRIALS REGISTRATION: NCT01030211.

  13. Rupasinghe D, Kiertiburanakul S, Kamarulzaman A, Zhang F, Kumarasamy N, Chaiwarith R, et al.
    HIV Med, 2020 07;21(6):397-402.
    PMID: 31852025 DOI: 10.1111/hiv.12836
    OBJECTIVES: Early mortality among those still initiating antiretroviral therapy (ART) with advanced stages of HIV infection in resource-limited settings remains high despite recommendations for universal HIV treatment. We investigated risk factors associated with early mortality in people living with HIV (PLHIV) starting ART at low CD4 levels in the Asia-Pacific.

    METHODS: PLHIV enrolled in the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) who initiated ART with a CD4 count  1 year were censored at 12 months. Competing risk regression was used to analyse risk factors with loss to follow-up as a competing risk.

    RESULTS: A total of 1813 PLHIV were included in the study, of whom 74% were male. With 73 (4%) deaths, the overall first-year mortality rate was 4.27 per 100 person-years (PY). Thirty-eight deaths (52%) were AIDS-related, 10 (14%) were immune reconstituted inflammatory syndrome (IRIS)-related, 13 (18%) were non-AIDS-related and 12 (16%) had an unknown cause. Risk factors included having a body mass index (BMI)  100 cells/μL: SHR 0.12; 95% CI 0.05-0.26) was associated with reduced hazard for mortality compared to CD4 count ≤ 25 cells/μL.

    CONCLUSIONS: Fifty-two per cent of early deaths were AIDS-related. Efforts to initiate ART at CD4 counts > 50 cell/μL are associated with improved short-term survival rates, even in those with late stages of HIV disease.

  14. Pozniak A, Bekker LG, Kamarulzaman A, Gandhi M, Horton R, Das P, et al.
    Lancet, 2020 05 23;395(10237):1598-1599.
    PMID: 32359401 DOI: 10.1016/S0140-6736(20)31026-6
  15. Chong YM, Sam IC, Ponnampalavanar S, Syed Omar SF, Kamarulzaman A, Munusamy V, et al.
    Microbiol Resour Announc, 2020 May 14;9(20).
    PMID: 32409547 DOI: 10.1128/MRA.00383-20
    We sequenced four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Malaysia during the second wave of infection and found unique mutations which suggest local evolution. Circulating Malaysian strains represent introductions from different countries, particularly during the first wave of infection. Genome sequencing is important for understanding local epidemiology.
  16. Ansari AW, Ahmad F, Shankar EM, Kong YY, Tan HY, Jacobs R, et al.
    PMID: 32398557 DOI: 10.1097/QAI.0000000000002399
    BACKGROUND: We have previously shown an association of elevated co-inhibitory molecule 2B4 expression with iNKT cells alterations in HIV disease. Herein we show a comparative analysis of 2B4 expression on iNKT cells of HIV long-term non-progressors (LTNPs) and progressors.

    METHODS: Anti-retroviral therapy (ART) naïve HIV-seropositive individuals (progressors, n=16) and long-term non-progressors (LTNPs, n=10) were recruited for this study. We employed multi-color flow cytometry on frozen peripheral blood mononuclear cells (PBMCs) to determine iNKT subset frequencies, the levels of co-inhibitory 2B4 expression, and intracellular IFN-γ production. CD1d tetramer was used to characterize iNKT cells.

    RESULTS: We report significantly lower level of 2B4 expression on bulk LTNPs iNKT cells as well as on their CD4 subsets compared to HIV progressors. Furthermore, the iNKT cells from LTNPs produced higher amount of IFN-γ than HIV progressors as detected by intracellular cytokine staining. Interestingly, the frequency of 2B4iNKT cells of progressors but not LTNPs significantly correlates with CD4 T cell count, HIV viral load and IFNγ production by iNKT cells.

    CONCLUSION: Our results suggest that in addition to suppressed HIV replication, diminished 2B4 expression and associated co-inhibitory signaling, and substantial production of IFN-γ could contribute to preserved iNKT cell phenotype in LTNPs.

  17. Boettiger DC, Law MG, Ross J, Huy BV, Heng B, Ditangco R, et al.
    Journal of virus eradication, 2020 Feb 20;6(1):11-18.
    PMID: 32175086
    Objectives: Integration of HIV and non-communicable disease services improves the quality and efficiency of care in low- and middle-income countries (LMICs). We aimed to describe current practices for the screening and management of atherosclerotic cardiovascular disease (ASCVD) among adult HIV clinics in Asia.

    Methods: Sixteen LMIC sites included in the International Epidemiology Databases to Evaluate AIDS - Asia-Pacific network were surveyed.

    Results: Sites were mostly (81%) based in urban public referral hospitals. Half had protocols to assess tobacco and alcohol use. Protocols for assessing physical inactivity and obesity were in place at 31% and 38% of sites, respectively. Most sites provided educational material on ASCVD risk factors (between 56% and 75% depending on risk factors). A total of 94% reported performing routine screening for hypertension, 100% for hyperlipidaemia and 88% for diabetes. Routine ASCVD risk assessment was reported by 94% of sites. Protocols for the management of hypertension, hyperlipidaemia, diabetes, high ASCVD risk and chronic ischaemic stroke were in place at 50%, 69%, 56%, 19% and 38% of sites, respectively. Blood pressure monitoring was free for patients at 69% of sites; however, most required patients to pay some or all the costs for other ASCVD-related procedures. Medications available in the clinic or within the same facility included angiotensin-converting enzyme inhibitors (81%), statins (94%) and sulphonylureas (94%).

    Conclusion: The consistent availability of clinical screening, diagnostic testing and procedures and the availability of ASCVD medications in the Asian LMIC clinics surveyed are strengths that should be leveraged to improve the implementation of cardiovascular care protocols.

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