ORCID Profile
0000-0001-5734-1672
Current Organisations
Wesley Medical Research
,
endosQ
,
Coral Sea Clinical Research Institute
,
Universiti Kebangsaan Malaysia
,
Universiti Kebangsaan Malaysia Fakulti Kejuruteraan dan Alam Bina
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Publications
High incidence of inflammatory bowel disease in Northern Australia: a prospective community population‐based Australian incidence study in the Mackay‐Isaac‐Whitsunday region
Publisher: Wiley
Date: 29-12-2022
DOI: 10.1111/IMJ.15941
Abstract: To determine the incidence of inflammatory bowel disease (IBD) in the Mackay‐Isaac‐Whitsunday region in Northern Queensland (−21.14° S) and to allow a comparison with Southern Australian and New Zealand data (Geelong, Australia −38.14° S Tasmania −41.43° S and −42.88° S (Launceston and Hobart) and Canterbury, New Zealand −43.46 °S). A prospective observational community population‐based IBD study was conducted between 1 June 2017 and 31 May 2018. Primary includes the crude annual incidence rate of IBD, Crohn's disease (CD), ulcerative colitis (UC) and inflammatory bowel disease‐unclassified (IBDU), while secondary includes disease phenotype and behaviour. Fifty‐six new cases of IBD were identified. Twenty‐three were CD, 30 were UC and 3 were IBDU. The crude annual incidence rate per 100 000 for IBD, CD, UC and IBDU were 32.2 (95% confidence interval (CI): 24.78–41.84), 13.23 (95% CI: 8.79–19.90), 17.25 (95% CI: 12.06–24.67) and 1.73 (95% CI: 0.56–5.35). When directly age‐standardised to the World Health Organisation Standard Population Distribution, the overall CD, UC and IBDU incidence were 13.19, 17.34 and 1.85 per 100 000, with an overall age‐standardised IBD incidence of 32.38. This is the first study to define the incidence of IBD in a Northern Australian cohort and to allow a comparison between North and Southern Australia. The IBD crude is the highest reported in Australia. Like others, we found a high and low incidence of upper gastrointestinal Crohn's disease and complicated disease at diagnosis respectively, likely reflective of the increased availability and early uptake of endoscopic procedures.
Randomised clinical trial: a placebo‐controlled study of subcutaneous or intradermal NEXVAX2, an investigational immunomodulatory peptide therapy for coeliac disease
Publisher: Wiley
Date: 13-08-2019
DOI: 10.1111/APT.15435
Abstract: Nexvax2 contains three gluten-derived peptides, intended to tolerize coeliac disease patients to gluten. Sequences cover six epitopes that trigger immune activation in human leucocyte antigen-DQ2.5-positive patients, most notably after an initial dose. Patients experience gastrointestinal symptoms with increases in serum interleukin-2. Consistent with Nexvax2's induction of non-responsiveness, reactivity disappears after repeated doses, or is avoided with gradual dose escalation. Early clinical trials used intradermal dosing, but pharmacokinetics and rapid onset of effect suggest that subcutaneous delivery may also be effective. To document the relative bioavailability of Nevax2 peptides after subcutaneous and intradermal dosing, and the tolerability and ability of subcutaneous dosing to induce non-responsiveness to Nexvax2 peptides. A randomised, double-blind, placebo-controlled study was conducted to assess plasma pharmacokinetics after subcutaneous and intradermal Nexvax2 dosing in HLA DQ2.5-positive patients, who had symptoms after an oral gluten challenge. Randomisation was to semi-weekly Nexvax2 (n = 12) or placebo (n = 2) injections, over a 5-week subcutaneous dose escalation and 2-week maintenance period, the latter with four doses of 900 µg, two subcutaneous and two intradermal. Post-dose circulating peptide and interleukin-2 levels were assessed. Investigators recorded adverse events experienced by patients. Subcutaneous dosing resulted in slightly greater exposure. Interleukin-2 responses were seen with the gluten challenge but not after subcutaneous or intradermal dosing of 900 µg. Adverse events were generally mild and self-limited. Subcutaneous and intradermal dosing of Nexvax2 yield similar bioavailability of constituent peptides subcutaneous dose escalation avoids an immune response to dominant gluten epitopes.
Masked bolus gluten challenge low in FODMAPs implicates nausea and vomiting as key symptoms associated with immune activation in treated coeliac disease.
Publisher: Wiley
Date: 26-11-2020
DOI: 10.1111/APT.15551
Abstract: In patients with coeliac disease, FODMAPs in gluten-containing foods, and participant anticipation of a harmful ('nocebo') effect, may contribute to acute symptoms after gluten challenge. To establish acute gluten-specific symptoms linked to immune activation in coeliac disease METHODS: We included 36 coeliac disease patients on a gluten-free diet receiving placebo in the RESET CeD trial. Double-blind, bolus vital wheat gluten (~6-g gluten protein) and sham challenges low in FODMAPs were consumed 2 weeks apart. Assessments included daily Coeliac Disease Patient Reported Outcome (CeD PRO) symptom scores (0-10), adverse events and serum interleukin-2 (baseline and 4 hours). Median CeD PRO score for nausea increased most (sham: 0 vs gluten: 5.5 P < .001). Apart from tiredness (1 vs 4, P = .005) and headache (0 vs 2, P = .002), changes in other symptoms were small or absent. Only nausea increased significantly in occurrence with gluten (11% vs 69%, P < .001). Without nausea, only tiredness and flatulence were common after gluten. Nausea (6% vs 61%, P < .001 median onset: 1:34 hours) and vomiting (0% vs 44%, P < .001 1:51 hours) were the only adverse events more common with gluten than sham. Interleukin-2 was always below the level of quantitation (0.5 pg/mL) at baseline, and after sham. Interleukin-2 was elevated after gluten in 97% of patients (median fold-change: 20), and correlated with severity of nausea (r Nausea and vomiting are relatively specific indicators of acute gluten ingestion, and correlate with immune activation. IBS-like symptoms without nausea are unlikely to indicate recent gluten exposure.
Small bowel endoscopy and coeliac disease.
Publisher: Elsevier BV
Date: 06-2012
Decolourisation of Real Industrial and Synthetic Textile Dye Wastewater Using Activated Dolomite
Publisher: MDPI AG
Date: 17-03-2023
DOI: 10.3390/W15061172
Abstract: Textile effluent accounts for 22% of the total industrial wastewater produced in Malaysia. Due to their ubiquitous use in organic dyes, inefficiently treated textile wastewaters pose environmental and health hazards. Colour, chemical oxygen demand, biochemical oxygen demand, toxic metals and microbes are the commonly targeted water quality parameters in untreated textile fluids. Furthermore, their non-biodegradability and high colour intensity may reduce aquatic ersity by blocking the sunlight. Recently, physical treatment, principally adsorption, has been conducted. Dolomite has additional features, such as performing as a heavy metal and microbe remover. This study employed dolomite for treating textile dye wastewater from a commercial textile manufacturer and synthetic effluent containing methyl orange. Different sizes of dolomite were activated at different temperatures and subsequently added to the water s les in varying amounts. After 2 h of agitation at 100 rpm and sedimentation for 24 h, their absorbance reading was taken. Their morphological, decolourisation percentage, chemical oxygen demand reduction percentage and bacterial growth post-treatment were examined. Despite variances in dolomite’s capacity to decolourise colours, the treatment proved effective in decolourising dyes, removing chemical oxygen demand and reducing bacterial growth. The most significant percentages of decolourisation observed were 98.7% for real textile dye wastewater (RTDW) and 78.0% for synthetic textile dye wastewater (STDW), while for chemical oxygen demand, reductions were 66.7% for RTDW and 73.9% for STDW, respectively. As for microbe growth inhibition, the highest growth reduction percentages were 99.7% and 98.6% for RTDW and STDW, respectively.
Elevated serum interleukin‐2 after gluten correlates with symptoms and is a potential diagnostic biomarker for coeliac disease
Publisher: Wiley
Date: 04-09-2019
DOI: 10.1111/APT.15477
Abstract: Coeliac disease patients on a gluten-free diet experience reactions to gluten, but these are not well characterised or understood. Systemic cytokine release was recently linked to reactivation of gluten immunity in coeliac disease. To define the nature and time-course of symptoms and interleukin-2 changes specific for coeliac disease patients. 25 coeliac disease patients on a gluten-free diet and 25 healthy volunteers consumed a standardised 6 gram gluten challenge. Coeliac Disease Patient-Reported Outcome survey and global digestive symptom assessment were completed hourly up to 6 hours after gluten. Adverse events over 48 hours were recorded. Serum interleukin-2 was measured at baseline, and 2, 4 and 6 hours. Serum interleukin-2 was always undetectable in healthy controls, whereas it was undetectable at baseline and elevated >0.5 pg/ml at 4 hours in 92% of coeliac disease patients. All patient-reported outcome severity scores increased significantly after gluten in coeliac disease patients (P < .001 Wilcoxon signed rank test), but not in controls. Symptoms began after 1 hour, and peaked in the third. Nausea and vomiting characterised severe reactions, but mild reactions were limited to headache and tiredness. Peak interleukin-2 correlated with symptom severity, particularly for nausea and vomiting. Serum interleukin-2 elevations correlate with timing and severity of symptoms after gluten in coeliac disease. Standardised bolus gluten food challenge and interleukin-2 assessment could provide a valuable clinical test to monitor and diagnose coeliac disease in patients established on a gluten-free diet.
Efficacy and safety of gluten peptide-based antigen-specific immunotherapy (Nexvax2) in adults with coeliac disease after bolus exposure to gluten (RESET CeD): an interim analysis of a terminated rand
Publisher: Elsevier BV
Date: 05-2023
Patient factors influencing acute gluten reactions and cytokine release in treated coeliac disease
Publisher: Springer Science and Business Media LLC
Date: 26-11-2020
DOI: 10.1186/S12916-020-01828-Y
Abstract: Patients with coeliac disease (CD) commonly report a variety of adverse symptoms to gluten, but descriptions of the symptomatic response in the literature may have been confounded by the presence of food components such as fermentable carbohydrates (FODMAPs) causing symptoms of irritable bowel syndrome independent of gluten. In recent unmasked and masked low FODMAP gluten challenge studies in small groups of treated CD patients, nausea and vomiting were shown to be the key symptoms associated with serum interleukin (IL)-2 release. Our objective was to utilise a large and erse cohort of people with CD undertaking a standardised gluten food challenge to characterise the demographic, genetic and clinical factors influencing the severity and timing of acute gluten reactions and IL-2 production. A total of 295 adults treated for CD were observed for 6 h after an unmasked food challenge consisting of 10 g vital wheat gluten (low in FODMAPs) in 100 ml water. Assessments included patient-reported outcomes, serum IL-2 and adverse events. Responses were analysed according to patient characteristics, HLA-DQ genotype, duodenal histology and response to a second gluten challenge. Peak symptom severity was at 3 h (median severity 5/10). Peak IL-2 was at 4 h (median 4 pg/ml, range undetectable to 1028 pg/ml). Older age, older age at diagnosis, HLA-DQ2.5 positivity and homozygosity for HLA-DQB1*02 were each significantly associated with IL-2 elevations after gluten. Patients positive for HLA-DQ2.5, DQ8, DQ2.2 or DQ7 showed elevated IL-2 after gluten. Patient factors were not significantly associated with severity of digestive symptoms, but symptoms were correlated to one another and serum IL-2. Gluten challenge after 5 months caused more vomiting and higher IL-2 levels, but responses correlated with the first. Gluten-induced symptoms and cytokine release is common in adults with treated CD. Age, genetics and previous response to gluten predict these acute reactions to gluten challenge. Structured symptom assessment and serum IL-2 after standardised gluten challenge may inform on patient diagnosis, the role of gluten in symptomatology and the need for adjunctive treatment. ClinicalTrials.gov , NCT03644069 Registered 21 May 2018.
Epitope-Specific Immunotherapy Targeting CD4-Positive T Cells in Celiac Disease: Safety, Pharmacokinetics, and Effects on Intestinal Histology and Plasma Cytokines with Escalating Dose Regimens of Nex
Publisher: Elsevier BV
Date: 12-2017
Serum cytokines elevated during gluten-mediated cytokine release in coeliac disease
Publisher: Oxford University Press (OUP)
Date: 10-2019
DOI: 10.1111/CEI.13369
Abstract: Cytokines have been extensively studied in coeliac disease, but cytokine release related to exposure to gluten and associated symptoms has only recently been described. Prominent, early elevations in serum interleukin (IL)-2 after gluten support a central role for T cell activation in the clinical reactions to gluten in coeliac disease. The aim of this study was to establish a quantitative hierarchy of serum cytokines and their relation to symptoms in patients with coeliac disease during gluten-mediated cytokine release reactions. Sera were analyzed from coeliac disease patients on a gluten free-diet (n = 25) and from a parallel cohort of healthy volunteers (n = 25) who underwent an unmasked gluten challenge. Sera were collected at baseline and 2, 4 and 6 h after consuming 10 g vital wheat gluten flour 187 cytokines were assessed. Confirmatory analyses were performed by high-sensitivity electrochemiluminescence immunoassay. Cytokine elevations were correlated with symptoms. Cytokine release following gluten challenge in coeliac disease patients included significant elevations of IL-2, chemokine (C-C motif) ligand 20 (CCL20), IL-6, chemokine (C-X-C motif) ligand (CXCL)9, CXCL8, interferon (IFN)-γ, IL-10, IL-22, IL-17A, tumour necrosis factor (TNF)-α, CCL2 and hiregulin. IL-2 and IL-17A were earliest to rise. Peak levels of cytokines were generally at 4 h. IL-2 increased most (median 57-fold), then CCL20 (median 10-fold). Cytokine changes were strongly correlated with one another, and the most severely symptomatic patients had the highest elevations. Early elevations of IL-2, IL-17A, IL-22 and IFN-γ after gluten in patients with coeliac disease implicates rapidly activated T cells as their probable source. Cytokine release after gluten could aid in monitoring experimental treatments and support diagnosis.
Epitope-specific immunotherapy targeting CD4-positive T cells in coeliac disease: two randomised, double-blind, placebo-controlled phase 1 studies
Publisher: Elsevier BV
Date: 07-2017
Characterising the Mucosal and Systemic Immune Responses to Experimental Human Hookworm Infection
Publisher: Public Library of Science (PLoS)
Date: 09-02-2012
Effect of Hookworm Infection on Wheat Challenge in Celiac Disease – A Randomised Double-Blinded Placebo Controlled Trial
Publisher: Public Library of Science (PLoS)
Date: 08-03-2011
Editorial: inaccuracies in attribution of symptoms due to gluten-not just in those with self-reported noncoeliac gluten sensitivity. Authors' reply.
Publisher: Wiley
Date: 14-01-2020
DOI: 10.1111/APT.15629
Suppression of Inflammatory Immune Responses in Celiac Disease by Experimental Hookworm Infection
Publisher: Public Library of Science (PLoS)
Date: 16-09-2011
Baseline quantitative histology in therapeutics trials reveals villus atrophy in most patients with coeliac disease who appear well controlled on gluten‐free diet
Publisher: Hindawi Limited
Date: 2020
DOI: 10.1002/YGH2.380
Related Organisations
Universiti Kebangsaan Malaysia Fakulti Kejuruteraan Dan Alam Bina
Location: Malaysia
Related Funding Activities
No related grants have been discovered for Zarimah Mohd Hanafiah.