Displaying publications 1 - 20 of 305 in total

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  1. Baral S, Rao A, Twahirwa Rwema JO, Lyons C, Cevik M, Kågesten AE, et al.
    medRxiv, 2021 Dec 15.
    PMID: 33442703 DOI: 10.1101/2021.01.07.21249419
    Background: COVID-19 has rapidly emerged as a global public health threat with infections recorded in nearly every country. Responses to COVID-19 have varied in intensity and breadth, but generally have included domestic and international travel limitations, closure of non-essential businesses, and repurposing of health services. While these interventions have focused on testing, treatment, and mitigation of COVID-19, there have been reports of interruptions to diagnostic, prevention, and treatment services for other public health threats.

    Objectives: We conducted a scoping review to characterize the early impact of COVID-19 on HIV, tuberculosis, malaria, sexual and reproductive health, and malnutrition.

    Methods: A scoping literature review was completed using searches of PubMed and preprint servers (medRxiv/bioRxiv) from January 1st to October 31st, 2020, using Medical Subject Headings (MeSH) terms related to SARS-CoV-2 or COVID-19 and HIV, tuberculosis, malaria, sexual and reproductive health, and malnutrition. Empiric studies reporting original data collection or mathematical models were included, and available data synthesized by region. Studies were excluded if they were not written in English.

    Results: A total of 1604 published papers and 205 preprints met inclusion criteria, including 8.2% (132/1604) of published studies and 10.2% (21/205) of preprints: 7.3% (68/931) on HIV, 7.1% (24/339) on tuberculosis, 11.6% (26/224) on malaria, 7.8% (13/166) on sexual and reproductive health, and 9.8% (13/132) on malnutrition. Thematic results were similar across competing health risks, with substantial indirect effects of the COVID-19 pandemic and response on diagnostic, prevention, and treatment services for HIV, tuberculosis, malaria, sexual and reproductive health, and malnutrition.

    Discussion: COVID-19 emerged in the context of existing public health threats that result in millions of deaths every year. Thus, effectively responding to COVID-19 while minimizing the negative impacts of COVID-19 necessitates innovation and integration of existing programs that are often siloed across health systems. Inequities have been a consistent driver of existing health threats; COVID-19 has worsened disparities, reinforcing the need for programs that address structural risks. The data reviewed here suggest that effective strengthening of health systems should include investment and planning focused on ensuring the continuity of care for both rapidly emergent and existing public health threats.

  2. Shankar EM, Velu V, Kamarulzaman A, Larsson M
    World J Virol, 2015 Feb 12;4(1):17-24.
    PMID: 25674514 DOI: 10.5501/wjv.v4.i1.17
    Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis.
  3. Oong XY, Chook JB, Ng KT, Chow WZ, Chan KG, Hanafi NS, et al.
    Virol J, 2018 05 23;15(1):91.
    PMID: 29792212 DOI: 10.1186/s12985-018-1005-8
    BACKGROUND: Human metapneumovirus (HMPV) is established as one of the causative agents of respiratory tract infections. To date, there are limited reports that describe the effect of HMPV genotypes and/or viral load on disease pathogenesis in adults. This study aims to determine the role of HMPV genetic diversity and nasopharyngeal viral load on symptom severity in outpatient adults with acute respiratory tract infections.
    METHODS: Severity of common cold symptoms of patients from a teaching hospital was assessed by a four-category scale and summed to obtain the total symptom severity score (TSSS). Association between the fusion and glycoprotein genes diversity, viral load (quantified using an improved RT-qPCR assay), and symptom severity were analyzed using bivariate and linear regression analyses.
    RESULTS: Among 81/3706 HMPV-positive patients, there were no significant differences in terms of demographics, number of days elapsed between symptom onset and clinic visit, respiratory symptoms manifestation and severity between different HMPV genotypes/sub-lineages. Surprisingly, elderly patients (≥65 years old) had lower severity of symptoms (indicated by TSSS) than young and middle age adults (p = 0.008). Nasopharyngeal viral load did not correlate with nor predict symptom severity of HMPV infection. Interestingly, at 3-5 days after symptom onset, genotype A-infected patients had higher viral load compared to genotype B (4.4 vs. 3.3 log10 RNA copies/μl) (p = 0.003).
    CONCLUSIONS: Overall, HMPV genetic diversity and viral load did not impact symptom severity in adults with acute respiratory tract infections. Differences in viral load dynamics over time between genotypes may have important implications on viral transmission.
    Study site: Primary Care Clinic, University of Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  4. Al-Khannaq MN, Ng KT, Oong XY, Pang YK, Takebe Y, Chook JB, et al.
    Virol J, 2016 Feb 25;13:33.
    PMID: 26916286 DOI: 10.1186/s12985-016-0488-4
    BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking.
    METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference.
    RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed.
    CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics.
    Study site: Primary Care Clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  5. Wang B, Lau KA, Ong LY, Shah M, Steain MC, Foley B, et al.
    Virology, 2007 Oct 25;367(2):288-97.
    PMID: 17604072
    The HIV protease-reverse transcriptase (PR-RT) (1047 bp), gp120-env (891 bp) and gp41-env (547 bp) regions from the plasma of 115 HIV-1-infected patients in Kuala Lumpur (KL), Malaysia were sequenced. Detailed phylogenetic and bootscanning analyses were performed to determine the mosaic structure of the HIV-1 strains and their recombination breakpoint(s). Among the 50 patient samples in which all three regions could be amplified, the HIV-1 CRF01_AE subtype (46%) was predominant followed by subtypes B (10%) and B' (6%). A total of 9/50 (18%) patients were infected with a CRF01_AE/B inter-subtype recombinant, displaying a recombinant form (RF)(PR-RT), CRF01_AE(gp120-env) and CRF01_AE(gp41-env). This RF was derived from the Thai variants of CRF01_AE and B' subtype, with two distinct B' subtype segments in the backbone of CRF01_AE, similar to the newly identified CRF33_01B. In addition, one sample demonstrated a close structural relationship with the new CRF33_01B in the PR-RT region but displayed B' segment in part of the env region (RF(PR-RT), CRF01_AE/B'(gp120-env) and B'(gp41-env)) indicating continuing evolution of CRF33_01B. The remaining 18% of samples were identified as unique recombinant forms (URFs).
  6. Jiamsakul A, Kerr SJ, Ng OT, Lee MP, Chaiwarith R, Yunihastuti E, et al.
    Trop Med Int Health, 2016 May;21(5):662-74.
    PMID: 26950901 DOI: 10.1111/tmi.12690
    OBJECTIVES: Treatment interruptions (TIs) of combination antiretroviral therapy (cART) are known to lead to unfavourable treatment outcomes but do still occur in resource-limited settings. We investigated the effects of TI associated with adverse events (AEs) and non-AE-related reasons, including their durations, on treatment failure after cART resumption in HIV-infected individuals in Asia.

    METHODS: Patients initiating cART between 2006 and 2013 were included. TI was defined as stopping cART for >1 day. Treatment failure was defined as confirmed virological, immunological or clinical failure. Time to treatment failure during cART was analysed using Cox regression, not including periods off treatment. Covariables with P < 0.10 in univariable analyses were included in multivariable analyses, where P < 0.05 was considered statistically significant.

    RESULTS: Of 4549 patients from 13 countries in Asia, 3176 (69.8%) were male and the median age was 34 years. A total of 111 (2.4%) had TIs due to AEs and 135 (3.0%) had TIs for other reasons. Median interruption times were 22 days for AE and 148 days for non-AE TIs. In multivariable analyses, interruptions >30 days were associated with failure (31-180 days HR = 2.66, 95%CI (1.70-4.16); 181-365 days HR = 6.22, 95%CI (3.26-11.86); and >365 days HR = 9.10, 95% CI (4.27-19.38), all P < 0.001, compared to 0-14 days). Reasons for previous TI were not statistically significant (P = 0.158).

    CONCLUSIONS: Duration of interruptions of more than 30 days was the key factor associated with large increases in subsequent risk of treatment failure. If TI is unavoidable, its duration should be minimised to reduce the risk of failure after treatment resumption.

  7. Earnshaw VA, Jin H, Wickersham J, Kamarulzaman A, John J, Altice FL
    Trop Med Int Health, 2014 Jun;19(6):672-679.
    PMID: 24666546 DOI: 10.1111/tmi.12306
    OBJECTIVES: Stigma towards people living with HIV/AIDS (PLWHA) is strong in Malaysia. Although stigma has been understudied, it may be a barrier to treating the approximately 81 000 Malaysian PLWHA. The current study explores correlates of intentions to discriminate against PLWHA among medical and dental students, the future healthcare providers of Malaysia.
    METHODS: An online, cross-sectional survey of 1296 medical and dental students was conducted in 2012 at seven Malaysian universities; 1165 (89.9%) completed the survey and were analysed. Socio-demographic characteristics, stigma-related constructs and intentions to discriminate against PLWHA were measured. Linear mixed models were conducted, controlling for clustering by university.
    RESULTS: The final multivariate model demonstrated that students who intended to discriminate more against PLWHA were female, less advanced in their training, and studying dentistry. They further endorsed more negative attitudes towards PLWHA, internalised greater HIV-related shame, reported more HIV-related fear and disagreed more strongly that PLWHA deserve good care. The final model accounted for 38% of the variance in discrimination intent, with 10% accounted for by socio-demographic characteristics and 28% accounted for by stigma-related constructs.
    CONCLUSIONS: It is critical to reduce stigma among medical and dental students to eliminate intentions to discriminate and achieve equitable care for Malaysian PLWHA. Stigma-reduction interventions should be multipronged, addressing attitudes, internalised shame, fear and perceptions of deservingness of care.
    KEYWORDS: HIV/AIDS; Malaisie; Malasia; Malaysia; VIH/SIDA; cuidados sanitarios profesionales; discriminación; discrimination; estigma; homosexuality; professional healthcare students; stigma; stigmatisation; substance abuse; étudiants en profession de soins de santé
  8. Al-Darraji HA, Altice FL, Kamarulzaman A
    Trop Med Int Health, 2016 Aug;21(8):1049-1058.
    PMID: 27197601 DOI: 10.1111/tmi.12726
    OBJECTIVES: To investigate the prevalence of previously undiagnosed active tuberculosis (TB) cases among prisoners in Malaysia's largest prison using an intensified TB case-finding strategy.

    METHODS: From October 2012 to May 2013, prisoners housed in two distinct units (HIV-negative and HIV-positive) were approached to participate in the TB screening study. Consenting prisoners submitted two sputum samples that were examined using GeneXpert MTB/RIF, smear microscopy and liquid culture. Socio-demographic and clinical information was collected and correlates of active TB, defined as having either a positive GeneXpert MTB/RIF or culture results, were assessed using regression analyses.

    RESULTS: Among the total of 559 prisoners, 442 (79.1%) had complete data; 28.7% were HIV-infected, 80.8% were men and the average age was 36.4 (SD 9.8) years. Overall, 34 (7.7%) had previously undiagnosed active TB, of whom 64.7% were unable to complete their TB treatment in prison due to insufficient time (<6 months) remaining in prison. Previously undiagnosed active TB was independently associated with older age groups (AOR 11.44 and 6.06 for age ≥ 50 and age 40-49 years, respectively) and with higher levels of immunosuppression (CD4 < 200 cells/ml) in HIV-infected prisoners (AOR 3.07, 95% CI 1.03-9.17).

    CONCLUSIONS: The high prevalence of previously undiagnosed active TB in this prison highlights the inadequate performance of internationally recommended case-finding strategies and suggests that passive case-finding policies should be abandoned, especially in prison settings where HIV infection is prevalent. Moreover, partnerships between criminal justice and public health treatment systems are crucial to continue TB treatment after release.

  9. Chong YB, Tan LP, Robinson S, Lim SK, Ng KP, Keng TC, et al.
    Trop Biomed, 2012 Jun;29(2):270-6.
    PMID: 22735849 MyJurnal
    Penicilliosis is a rare occurrence among non human immunodeficiency virus (HIV) infected patients. We report here two cases of Penicillium marneffei infection in patients with systemic lupus erythematosus (SLE). Both patients had a recent flare of lupus and were on immunosuppressive drugs when they presented with prolonged fever without an obvious foci of infection, unresponsive to broad-spectrum antibiotics. They were leucopaenic upon admission, with rapid deterioration during the course of the illness. Diagnosis of penicilliosis via fungal isolation from blood culture was delayed resulting in the late initiation of antifungal agents. While both patients ultimately recovered, the delay in diagnosis led to a prolonged hospital stay with increased morbidity. Clinicians should be aware of this uncommon but emerging fungal pathogen in SLE patients and maintain a high index of suspicion in diagnosing this potentially fatal but treatable disease.
  10. 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.
  11. 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.
  12. Tan SY, Tan LH, Teo SM, Thiruventhiran T, Kamarulzaman A, Hoh HB
    Transplant Proc, 2000 Nov;32(7):1965-6.
    PMID: 11120022
  13. Mohd Sani N, Aziz Z, Kamarulzaman A
    Ther Innov Regul Sci, 2021 05;55(3):490-502.
    PMID: 33231863 DOI: 10.1007/s43441-020-00243-y
    INTRODUCTION: Biosimilars are a cost-effective alternative to original biologic medicines that allow patients access to biologic therapies for various chronic diseases. Our paper aims to provide an overview of biosimilars in Malaysia with emphasis on the comparison of Malaysian guidelines with guidelines from well-established regulatory agencies, a review of biosimilars' market approval and their reported adverse effects (AEs) as well as clinical trials conducted in Malaysia.

    METHODS: We searched the official websites of the National Pharmaceutical Regulatory Agency (NPRA) Malaysia and three other well-established agencies, online databases of Medline® and EMBASE for guidelines on legislation and regulations of biosimilars. Meanwhile, we extracted the reports of AEs involving biosimilars in Malaysia from the NPRA database and for global AEs from the World Health Organisation VigyLize database. The ClinicalTrials.gov Website by the U.S. National Library of Medicines was the source for data on clinical trials.

    RESULTS: Malaysia followed the principles of the European Medicines Agency biosimilar regulations and issued their guideline in 2008. Since then, NPRA has approved 24 biosimilar products and recorded 499 AE reports, of which 43 (8.6%) were serious. NPRA has also approved ten Phase III clinical trials in Malaysia with four trials still ongoing.

    CONCLUSION: Malaysia follows a stringent regulatory pathway for the approval of biosimilars enacted by well-established regulatory agencies to maintain the quality, efficacy and safety of biosimilars. Introducing biosimilars to the Malaysian market would improve patients' accessibility to biologic therapies.

  14. Margolis B, Al-Darraji HA, Wickersham JA, Kamarulzaman A, Altice FL
    Int J Tuberc Lung Dis, 2013 Dec;17(12):1538-44.
    PMID: 24200265 DOI: 10.5588/ijtld.13.0193
    There are currently no routine screening procedures for active tuberculosis (TB) or latent tuberculous infection (LTBI) in Malaysian prisons.
  15. Al-Darraji HA, Kamarulzaman A, Altice FL
    Int J Tuberc Lung Dis, 2012 Jul;16(7):871-9.
    PMID: 22410101 DOI: 10.5588/ijtld.11.0447
    Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide and the main cause of death in correctional facilities in middle- and low-income countries. Due to the closed environment and the concentration of individuals with TB-related risk factors, effective measures are required to control TB in such settings. Isoniazid preventive therapy (IPT) represents an effective and cost-effective measure. Despite international recommendations that IPT be integral to TB control, it is seldom deployed. A systematic review of interventions used to assess IPT initiation and completion in correctional facilities was conducted using published studies from two biomedical databases and relevant keywords. Additional references were reviewed, resulting in 18 eligible studies. Most (72%) studies were conducted in the United States and in jail settings (60%), with the main objective of improving completion rates inside the facility or after release. Studies that provided data about initiation and completion rates showed poor success in correctional facilities. Adverse consequences and treatment interruption ranged from 1% to 55% (median 5%) in reported studies; hepatotoxicity was the most prevalent adverse reaction. Despite its accelerating effect on the development of active TB, information on human immunodeficiency virus (HIV) status was provided in only half of the studies. Among the four studies where IPT effectiveness was assessed, the results mirror those described in community settings. Future studies require thorough assessments of IPT initiation and completion rates and adverse effects, particularly in low- and middle-income countries and where comorbid viral hepatitis may contribute significantly to outcomes, and in settings where TB and HIV are more endemic.
  16. Goh KJ, Tan CT, Chew NK, Tan PS, Kamarulzaman A, Sarji SA, et al.
    N Engl J Med, 2000 Apr 27;342(17):1229-35.
    PMID: 10781618 DOI: 10.1056/NEJM200004273421701
    BACKGROUND: Between September 1998 and June 1999, there was an outbreak of severe viral encephalitis due to Nipah virus, a newly discovered paramyxovirus, in Malaysia.
    METHODS: We studied the clinical features of the patients with Nipah virus encephalitis who were admitted to a medical center in Kuala Lumpur. The case definition was based on epidemiologic, clinical, cerebrospinal fluid, and neuroimaging findings.
    RESULTS: Ninety-four patients with Nipah virus infection were seen from February to June 1999 (mean age, 37 years; ratio of male patients to female patients, 4.5 to 1). Ninety-three percent had had direct contact with pigs, usually in the two weeks before the onset of illness, suggesting that there was direct viral transmission from pigs to humans and a short incubation period. The main presenting features were fever, headache, dizziness, and vomiting. Fifty-two patients (55 percent) had a reduced level of consciousness and prominent brain-stem dysfunction. Distinctive clinical signs included segmental myoclonus, areflexia and hypotonia, hypertension, and tachycardia and thus suggest the involvement of the brain stem and the upper cervical spinal cord. The initial cerebrospinal fluid findings were abnormal in 75 percent of patients. Antibodies against Hendra virus were detected in serum or cerebrospinal fluid in 76 percent of 83 patients tested. Thirty patients (32 percent) died after rapid deterioration in their condition. An abnormal doll's-eye reflex and tachycardia were factors associated with a poor prognosis. Death was probably due to severe brain-stem involvement. Neurologic relapse occurred after initially mild disease in three patients. Fifty patients (53 percent) recovered fully, and 14 (15 percent) had persistent neurologic deficits.
    CONCLUSIONS: Nipah virus causes a severe, rapidly progressive encephalitis with a high mortality rate and features that suggest involvement of the brain stem. The infection is associated with recent contact with pigs.
  17. Abdool Karim SS, Barre-Sinoussi F, Varmus HE, Serwadda D, Bukusi E, M'boup S, et al.
    N Engl J Med, 2023 Sep 28;389(13):1159-1161.
    PMID: 37694893 DOI: 10.1056/NEJMp2310330
  18. Koh KC, Kamarulzaman A
    Med J Malaysia, 2011 Dec;66(5):491-4.
    PMID: 22390108 MyJurnal
    Community-based HIV voluntary counseling and testing (VCT) services is an effective alternative for mapping the local demographics of at-risk populations for HIV as well as provide an acceptable and reliable means of early detection of HIV. We describe the profiles of men-who-have-sex-with-men (MSM) who sought VCT services in a community based centre in Kuala Lumpur.
  19. Gan GG, Kamarulzaman A, Goh KY, Ng KP, Na SL, Soo-Hoo TS
    Med J Malaysia, 2002 Mar;57(1):118-22.
    PMID: 14569730
    We report a case of an invasive infection with non-sporulating Chrysosporium species in a patient who was treated with chemotherapy for relapsed acute lymphoblastic leukemia. This patient presented with a persistent lobar pneumonia, skin lesions, and possible involvement of the central nervous system. The patient responded to treatment with amphotericin B and oral itraconazole.
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