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In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV.STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA12 IU/mL in Thailand and HCV RNA15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183.Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment.In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.

IntroductionTo achieve the elimination of hepatitis C virus (HCV), substantial scale-up in access to testing and treatment is needed. This will require innovation and simplification of the care pathway, through decentralisation of testing and treatment to primary care settings and task-shifting to non-specialists. The objective of this study was to evaluate the feasibility and effectiveness of decentralisation of HCV testing and treatment using rapid diagnostic tests (RDTs) in primary healthcare clinics (PHCs) among high-risk populations, with referral of seropositive patients for confirmatory viral load testing and treatment.MethodsThis observational study was conducted between December 2018 and October 2019 at 25 PHCs in three regions in Malaysia. Each PHC was linked to one or more hospitals, for referral of seropositive participants for confirmatory testing and pretreatment evaluation. Treatment was provided in PHCs for non-cirrhotic patients and at hospitals for cirrhotic patients.ResultsDuring the study period, a total of 15 366 adults were screened at the 25 PHCs, using RDTs for HCV antibodies. Of the 2020 (13.2%) HCV antibody-positive participants, 1481/2020 (73.3%) had a confirmatory viral load test, 1241/1481 (83.8%) were HCV RNA-positive, 991/1241 (79.9%) completed pretreatment assessment, 632/991 (63.8%) initiated treatment, 518/632 (82.0%) completed treatment, 352/518 (68.0%) were eligible for a sustained virological response (SVR) cure assessment, 209/352 (59.4%) had an SVR cure assessment, and SVR was achieved in 202/209 (96.7%) patients. A significantly higher proportion of patients referred to PHCs initiated treatment compared with those who had treatment initiated at hospitals (71.0% vs 48.8%, pConclusionsThis study demonstrated the effectiveness and feasibility of a simplified decentralised HCV testing and treatment model in primary healthcare settings, targeting high-risk groups in Malaysia. There were good outcomes across most steps of the cascade of care when treatment was provided at PHCs compared with hospitals.

Background Health Research Priority Setting (HRPS) in the Ministry of Health (MOH) Malaysia was initiated more than a decade ago to drive effort toward research for informed decision and policy-making. This study assessed the impact of funded prioritised research and identified research gaps to inform future priority setting initiatives for universal access and quality healthcare in Malaysia. Methods Research impact of universal access and quality healthcare projects funded by the National Institutes of Health Malaysia were assessed based on the modified Payback Framework, addressing categories of informing policy, knowledge production, and benefits to health and health sector. For the HRPS process, the Child Health and Nutrition Research Initiative methodology was adapted and adopted, with the incorporation of stakeholder values using weights and monetary allocation survey. Workshop discussions and interviews with stakeholders and research groups were conducted to identify research gaps, with the use of conceptual frameworks to guide the search. Results Seventeen ongoing and 50 completed projects were identified for research funding impact analysis. Overall, research fund allocation differed from stakeholders’ expectation. For research impact, 48 out of 50 completed projects (96.0%) contributed to some form of policy-making efforts. Almost all completed projects resulted in outputs that contributed to knowledge production and were expected to lead to health and health sector benefits. The HRPS process led to the identification of research priority areas that stemmed from ongoing and new issues identified for universal access and quality healthcare. Conclusion The concerted efforts of evaluation of research funding impact, prioritisation, dissemination and policy-maker involvement were valuable for optimal health research resource utilisation in a resource constrained developing country. Embedding impact evaluation into a priority setting process and funding research based on national needs could facilitate health research investment to reach its potential. Electronic supplementary material The online version of this article (10.1186/s12913-019-4072-7) contains supplementary material, which is available to authorized users.

Background In 2006, 4 years of planning was started by the Ministry of Health, Malaysia (MOH), to implement the HPV (human papillomavirus) vaccination programme. An inter-agency and multi-sectoral collaborations were developed for Malaysia’s HPV school-based immunisation programme. It was approved for nationwide school base implementation for 13-year-old girls or first year secondary students in 2010. This paper examines how the various strategies used in the implementation over the last 7 years (2010–2016) that unique to Malaysia were successful in achieving optimal coverage of the target population. Methods Free vaccination was offered to school girls in secondary school (year seven) in Malaysia, which is usually at the age of 13 in the index year. All recipients of the HPV vaccine were identified through school enrolments obtained from education departments from each district in Malaysia. A total of 242,638 girls aged between 12 to 13 years studying in year seven were approached during the launch of the program in 2010. Approximately 230,000 girls in secondary schools were offered HPV vaccine per year by 646 school health teams throughout the country from 2010 to 2016. Results Parental consent for their daughters to receive HPV vaccination at school was very high at 96–98% per year of the programme. Of those who provided consent, over 99% received the first dose each year and 98–99% completed the course per year. Estimated population coverage for the full vaccine course, considering also those not in school, is estimated at 83 to 91% per year. Rates of adverse events reports following HPV vaccination were low at around 2 per 100,000 and the majority was injection site reactions. Conclusion A multisectoral and integrated collaborative structure and process ensured that the Malaysia school-based HPV immunisation programme was successful and sustained through the programme design, planning, implementation and monitoring and evaluation. This is a critical factor contributing to the success and sustainability of the school-based HPV immunisation programme with very high coverage.

Additional file 1: Supplementary Table 1. Overall concordance rate of HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genes in the control group, stratified by ethnicity. Supplementary Table 2. Classical 2-digit HLA alleles imputation accuracy in the control group, stratified by ethnicity. Supplementary Table 3. Classical 4-digit HLA alleles imputation accuracy in the control group, stratified by ethnicity. Supplementary Table 4. Number of imputed classical HLA alleles and amino acid polymorphisms achieved published genome-wide threshold of p

OBJECTIVE The association between human leukocyte antigen (HLA)-B*58:01 and risk of allopurinol-induced severe cutaneous adverse reactions (AIS) was observed across different populations. We explore the association between HLA-B*58:01 and AIS risk in multiethnic Malaysian population. The HLA-B*58:01 risk for different AIS clinical phenotypes and ethnicity was determined. METHODS We performed a case-control association study by genotyping the HLA-B alleles of 55 patients with AIS [11 toxic epidermal necrolysis (TEN), 21 Steven Johnson syndrome (SJS) 22 drug reaction wit eosinophilia and systemic symptoms (DRESS) and one acute generalized exanthematous pustulosis (AGEP)] and 42 allopurinol-tolerant controls (ATC). RESULTS HLA-B*58:01 was positive in 89.1 and 14.3% of the AIS and ATC study groups [odds ratio (OR) = 49.0, 95% confidence interval (CI) = 14.6-164.4, P < 0.0001)], respectively. Our data showed that 93.8% of the AIS-SJS/TEN patients and 86.4% of the AIS-DRESS patients were HLA-B*58:01 positive (AIS-SJS/TEN, OR = 90, 95% CI = 16.9-470.1, P < 0.0001 and AIS-DRESS OR = 38, 95% CI = 8.5-169.2, P < 0.0001). Stratification by ethnicity and clinical phenotypes revealed a significant increased risk between HLA-B*58:01 and Chinese-AIS patients (OR = 137.5, 95% CI = 11.3-1680.2, P < 0.0001), in particular Chinese patients with AIS-SJS/TEN phenotype (100% HLA-B*58:01 positive). HLA-B*58:01 was positive in 90.9% Chinese AIS-DRESS (P < 0.0001). Highly significant associations of HLA-B*58:01 were observed in Malay AIS-SJS/TEN (OR = 78, 95% CI = 9.8-619.9, P < 0.0001) and Malay AIS-DRESS (OR = 54, 95% CI = 6.6-442.9, P < 0.0001). Although the number of Indian-AIS patients was relatively small (n = 2), both were HLA-B*58:01 positive. CONCLUSION Our data suggest strong associations between HLA-B*58:01 and AIS in Malaysian population with Chinese and Malays ethnicity. The strong association was also observed in three different clinical phenotypes of AIS, mainly the AIS-SJS/TEN.

Background: In low- and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic NS5A inhibitor, and sofosbuvir has shown efficacy and safety in chronically HCV infected patients with genotype (GT) 4. The STORM-C-1 trial aims to assess the efficacy and safety of sofosbuvir plus ravidasvir in a more diverse population of adults chronically infected with HCV. Methods: STORM-C-1 is a two-stage, open-label, multicentre clinical trial in Malaysia and Thailand. HCV infected subjects with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-F3) were eligible to participate, regardless of HCV genotype, HIV infection status, prior interferon-based HCV treatment or source of HCV infection. Stage 1 results are reported here. Once-daily ravidasvir (200mg) and sofosbuvir (400mg) were prescribed for 12 (without cirrhosis) or 24 (with cirrhosis) weeks. The primary endpoint was sustained virologic response at 12 weeks post-treatment (SVR12). This trial is registered with ClinicalTrials.gov: NCT02961426 and the National Medical Research Register of Malaysia NMRR-16-747-29183. Findings: Between October 2016 and June 2017, 301 subjects were enrolled and 300 included in the full analysis set: 97 with GT1a, 27 GT1b, 2 GT2, 158 GT3, and 16 GT6; 81 (27%) had compensated cirrhosis; 90 (30%) had HIV co-infection; and 99 (33%) had prior interferon-based treatment. 291/300 subjects (97%, 95% CI 94%-99%) achieved SVR12. Three subjects prematurely discontinued study treatment due to adverse events. There were no deaths or treatment discontinuations due to the study drugs. Interpretation: In this first stage, ravidasvir plus sofosbuvir was found to be highly effective and well tolerated in all subgroups of this diverse adult population chronically infected with HCV. Trial Registration Number: This trial is registered with ClinicalTrials.gov: NCT02961426 and the National Medical Research Register of Malaysia NMRR-16-747-29183. Funding: Drugs for Neglected Diseases initiative; National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia. Conflict of Interest: Dr. Avihingsanon reports grants from National Science and Technology Development Agency (NSTDA) during the conduct of the study, and also from ViiV Healthcare outside of thesubmitted work. Tim Cressey and Nicolas Salvadori report a service agreement with DNDi.Isabelle Andrieux-Meyer, Caroline Menetrey, Francois Simon, Jean-Michel Piedagnel,Sasikala Siva, Alistair Swanson, Francois Bompart, Vishal Goyal, and Bernard Pecoul are employed by the Drugs for Neglected Diseases initiative. All other authors do not report any potential conflicts of interest. Ethical Approval: The initial protocol and all protocol amendments were reviewed and approved before implementation by the applicable individual institutional or national ethics committees. All subjects provided written informed consent.

Objective: The present review aimed to determine the effect of palm oil versus other oils on changes in body weight or Body Mass Index (BMI). Design: A systematic review was conducted. Studies were identified by database searching (EMBASE, PUBMED, CENTRAL, SCOPUS, PROQUEST, Web of Science [ISI Web of Knowledge], Cumulative Index to Nursing and Allied Health Library (CINAHL Plus), LILAC and ClinicalTrials.gov. Searching, selecting and reporting were done according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) Statement. Setting: Palm oil vs other oils intervention study on weight or BMI changes. Subjects: Individuals participating in palm oil vs other oil intervention study. Results: A total of 182 studies were screened for eligibility, five studies were finally included. Three studies compared the effect of palm oil vs sunflower oil on weight changes and BMI. One study examined the effect of hybrid palm oil vs extra virgin olive oil on weight changes. The last study examined the effect of palm oil vs olive oil vs lard on weight changes. Out of 292 participants in five studies, only one study (Iggman, 2014) had a low risk of bias. In this study, there was no significant difference between the group that received sunflower oil and palm oil (SMD: 0.04, 95% CI: -0.59 to 0.66). Other four studies had unclear risk of bias. Conclusions: Based on the review, there is insufficient evidence to suggest the impact of palm oil intake on weight changes or BMI.

Background: This study aims to determine the hazard ratio of having any complication from diabetes mellitus, and the associations between comorbidities and risk of having any complications from diabetes mellitus among diabetic patients who have attended government primary care clinics. Methods: Secondary data were retrieved from the Malaysian National Diabetic Registry which included all patients who received care. The data from the study on the socio-demographic, diabetes complications, clinical and treatment characteristics were analyzed using descriptive statistics. Cox regression was performed to estimate the hazard ratio for comorbidities, tobacco use, duration of diabetes and socio-demography characteristics upon time to diabetic complications. Results: Adjusted for other covariates, increase number of comorbidities contributed the highest hazard ratio risk: 1 comorbid (aHR: 2.47, 95% CI: 2.39, 2.55), 2 comorbidities (aHR: 4.34, 95% CI: 4.22, 4.47), 3 comorbidities (aHR: 6.56, 95% CI: 6.31, 6.81) and 4 comorbidities (aHR: 9.13, 95% CI: 8.20, 10.17). Other factors: age > 40 years (8%) Malays (27%) and smokers (10%) have hazard risks to develop diabetic complications. Conclusions: Increase in number of comorbidities will increase the risk of getting diabetes complications. Other factors such as age, gender, race, smoking status and duration of diabetes are also noted to contribute to increase risk for diabetes complications.

Objective Antibodies to the citrullinated protein antigens (ACPAs) are important in the diagnosis and pathogenesis of rheumatoid arthritis (RA). However, the prevalence of ACPAs with different fine specificities in different populations is unclear. This study sought to examine the fine specificity of the antibody responses toward citrullinated proteins in RA patients from Malaysia, an area where genetic and environmental determinants of RA are different from those in more frequently studied cohorts of Caucasian subjects. Methods A multiplex analytic microarray system was used to analyze the occurrence of antibodies to 10 different citrullinated peptides (filaggrin [fil307–324], vimentin [Vim2–17, Vim60–75], fibrinogen [Fibα563–583, Fibα580–600, Fibβ36–52, Fibβ62–81a, Fibβ62–81b], enolase [Eno5–21], and type II collagen [CitCII355–378]) in serum samples from 4,089 RA patients (1,231 Malaysian and 2,858 Swedish) and 827 healthy control subjects (249 Malaysian and 578 Swedish). The positive reaction threshold for each peptide was set separately for each population based on a specificity of 98%. Results Distinct differences in the frequencies of 5 ACPA fine specificities (Vim60–75, Vim2–17, Fibβ62–81b, Eno5–21, and CitCII355–378) were found between the Malaysian and Swedish RA populations, despite a nearly identical percentage of patients in each population who were positive for anti–cyclic citrullinated peptide 2 antibodies. In Malaysian RA patients compared with Swedish RA patients, the frequencies of antibodies to Vim60–75 (54% versus 44%, corrected P [P corr] = 1.06 × 10−8) and CitCII355–378 (17% versus 13%, P corr = 0.02) were significantly higher, while the frequencies of antibodies to Vim2–17 (25% versus 32%, P corr = 1.91 × 10−4), Fibβ62–81b (15% versus 30%, P corr = 2.47 × 10−22), and Eno5–21 (23% versus 50%, P corr = 3.64 × 10−57) were significantly lower. Conclusion Serum ACPA fine specificities differ between RA patients in different populations, although the total proportions of individuals positive for ACPAs are similar. Differing patterns of ACPA fine specificity could be attributed to variations in genetic and/or environmental factors.

Prawn allergy is a common cause of allergic reactions in countries where crustacean is a famous seafood. Macrobrachium rosenbergii (giant river prawn) is declared as a local major food allergens, causes severe symptoms like asthma and anaphylactic shock. Therefore, the goal concerning this research is to identify the allergenicity of heat treated of M. rosenbergii. Prawn extracts have been prepared using fresh raw prawn and three heat-treated prawn flesh (boiled, steamed, fried), then afterward analyzed by the usage of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in conformity with their protein profiles. Allergenic proteins were identified by means of immunoblotting by the use of sera from 30 prawn-allergic patients. The identities of selective major allergens were then determined by mass-spectrometry analysis. The raw prawn has 27 protein fractions between 6 to 207 kDa, while the heat-treated prawns have reduced number of protein bands. Six prominent bands at 72, 65, 48, 38, 36, and 30 kDa were considered as the major allergens of raw extract. Meanwhile, after heat remedies applied, most of the IgE-binding bands were disappeared except for three major allergens at 38, 36 or 30 kDa which were still remain to be seen, suggesting as highly thermostable allergens. Among heat-treated prawns, steamed and boiled elicited more allergenic bands, contrast to fried prawn extract. Mass spectrometry analysis identified two selected major allergens at 36 and 48 kDa as tropomyosin and arginine kinase, respectively. As a conclusion, this study indicated that both thermostable and thermolabile proteins from M. rosenbergii were allergenic. Tropomyosin and arginine kinase were identified as the most important major allergens. Thus, the knowledge on thermostability of prawn allergens are crucial for improving diagnosis and management of prawn allergic patients in this county.

Background Amid the current burden of non-communicable (NCD) diseases in Malaysia, there is a growing demand for more efficient service delivery of primary healthcare. A complex intervention is proposed to improve NCD management in Malaysia. This exploratory study aimed to assess primary healthcare providers’ receptiveness towards change prior to implementation of the proposed complex intervention. Method This study was conducted using an exploratory qualitative approach on purposely selected healthcare providers at primary healthcare clinics. Twenty focus group discussions and three in-depth interviews were conducted using a semi-structured interview guide. Consent was obtained prior to interviews and for audio-recordings. Interviews were transcribed verbatim and thematically analysed, guided by the Consolidated Framework for Implementation Research (CFIR), a framework comprised of five major domains promoting implementation theory development and verification across multiple contexts. Results The study revealed via CFIR that most primary healthcare providers were receptive towards any proposed changes or intervention for the betterment of NCD care management. However, many challenges were outlined across four CFIR domains—intervention characteristics, outer setting, inner setting, and individual characteristics—that included perceived barriers to implementation. Perception of issues that triggered proposed changes reflected the current situation, including existing facilitating aspects that can support the implementation of any future intervention. The importance of strengthening the primary healthcare delivery system was also expressed. Conclusion Understanding existing situations faced at the primary healthcare setting is imperative prior to implementation of any intervention. Healthcare providers’ receptiveness to change was explored, and using CFIR framework, challenges or perceived barriers among healthcare providers were identified. CFIR was able to outline the clinics’ setting, individual behaviour and external agency factors that have direct impact to the organisation. These are important indicators in ensuring feasibility, effectiveness and sustainability of any intervention, as well as future scalability considerations. Electronic supplementary material The online version of this article (10.1186/s12913-019-4312-x) contains supplementary material, which is available to authorized users.

Background Arthralgia is one of the common symptoms seen in RA and in mosquito-borne viral diseases (dengue and chikungunya infections). Studies have reported that both dengue and chikungunya infections are associated with long-term persistent rheumatic symptoms including joints, muscle and bone pain. Objectives We investigated the association between anti-dengue IgG antibody positivity and risk of developing anti-citrullinated peptide antibody (ACPA)-positive and ACPA-negative RA in the multi-ethnic Malaysian population. Methods A total of 1147 early RA cases (515 Malay, 254 Chinese and 378 Indians) and 1519 age, sex and residential area matched population-based controls (1,023 Malay, 208 Chinese, and 288 Indians) were included in this study. Anti-dengue IgG antibody was determined by ELISA method. The presence of anti-dengue IgG antibody and risk of developing ACPA-positive/ACPA-negative RA were estimated by calculating the odds ratio (OR) with 95% confidence interval (95% CI). Results Our data demonstrated that 79.1% (n=1,003) and 77.1% (n=1,255) RA and control subjects were positive for anti-dengue IgG antibody, respectively. Data analysis revealed that the Chinese RA patients has highest frequency of anti-dengue IgG antibody (86.6%) followed by the Indian (80.4%) and Malay (74.4%) RA patients while 83.7%, 87.5% and 73% Chinese, Indian and Malay healthy controls were positive for this antibody, respectively. The anti-dengue IgG antibody positivity was significantly associated with decreased risk of RA in the Indian population (OR 0.59, 95% CI: 0.38–0.91, p=0.02) and particularly for the ACPA-positive subset of RA (OR 0.60, 95% CI 0.37–0.96, p=0.03). Interestingly, we observed a non-significant increased risk for ACPA-positive RA in the Chinese (OR 1.49, 95% CI 0.81–2.72) and Malay populations (OR 1.06, 95% CI: 0.79–1.41) with anti-dengue IgG antibody. No association was observed between ACPA-negative RA and the antibody positivity. Conclusions Our study describes the association between anti-dengue IgG antibody occurrence and ACPA-positive RA, but not ACPA-negative RA in an ethnicity-dependent manner. Future research is needed to explore the biological mechanisms behind these findings. References [1] Mohd Zim MA, et al. Chikungunya infection in Malaysia: Comparison with dengue infection in adults and predictors of persistent arthralgia. Journal of Clinical Virology2013;56(2013):141–145. [2] Gissel Garci et al. Long-term persistence of clinical symptoms in dengue-infected persons and its association with immunological disorders. International Journal of Infectious Diseases2011;15(2011):e38–e43. Disclosure of Interest None declared

ANTI-COLLAGEN TYPE II ANTIBODIES ARE ASSOCIATED WITH EARLY INFLAMMATION IN MALAYSIAN RHEUMATOID ARTHRITIS PATIENTS WITH THREE DIFFERENT ETHINICITIES

Objectives. To identify the major allergenic proteins of clam (Paphia textile) and to investigate the effect of different cooking methods on the allergenicity of these identified proteins.Methods. Clam protein extracts were separated by denaturing polyacrylamide gel electrophoresis. IgE reactive proteins were then analyzed by immunoblotting with sera from patients with positive skin prick tests (SPT) to the raw clam extract. Mass spectrometry was used to identify the major allergenic proteins of this clam.Results. Raw extract showed 12 protein bands (18–150 kDa). In contrast, fewer protein bands were seen in the boiled extract; those ranging from 40 to 150 kDa were denatured. The protein profiles were similarly altered by frying or roasting. The immunoblots of raw and boiled extracts yielded 10 and 2 IgE-binding proteins, respectively. The fried and roasted extracts showed only a single IgE-binding protein at 37 kDa. Mass spectrometry analysis of the 37 and 42 kDa major allergens indicated that these spots were tropomyosin and actin, respectively.Conclusion. The two major allergens ofPaphia textilewere identified as the thermostable tropomyosin and a new thermolabile allergen actin.

Background Multiple factors, including interactions between genetic and environmental risks, are important in susceptibility to rheumatoid arthritis (RA). However, the underlying mechanism is not fully understood. This study was undertaken to evaluate whether DNA methylation can mediate the interaction between genotype and smoking in the development of anti-citrullinated peptide antibody (ACPA)-positive RA. Methods We investigated the gene-smoking interactions in DNA methylation using 393 individuals from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA). The interaction between rs6933349 and smoking in the risk of developing ACPA-positive RA was further evaluated in a larger portion of the EIRA (1119 controls and 944 ACPA-positive patients with RA), and in the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) (1556 controls and 792 ACPA-positive patients with RA). Finally, mediation analysis was performed to investigate whether DNA methylation of cg21325723 mediates this gene-environment interaction on the risk of developing of ACPA-positive RA. Results We identified and replicated one significant gene-environment interaction between rs6933349 and smoking in DNA methylation of cg21325723. This gene-smoking interaction is a novel interaction in the risk of developing ACPA-positive in both Caucasian (multiplicative P value = 0.056; additive P value = 0.016) and Asian populations (multiplicative P value = 0.035; additive P value = 0.00027), and it is mediated through DNA methylation of cg21325723. Conclusions We showed that DNA methylation of cg21325723 can mediate the gene-environment interaction between rs6933349 and smoking, impacting the risk of developing ACPA-positive RA, thus being a potential regulator that integrates both internal genetic and external environmental risk factors. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1276-2) contains supplementary material, which is available to authorized users.

Aim of Work: Initial observations implied IgG rheumatoid factor (RF) to be common among Malaysian rheumatoid arthritis (RA) patients. We tested this hypothesis and used a multiethnic RA cohort (Malays, Chinese and Indians) to investigate whether the IgG RF predominance might be genetically or environmentally determined. Patients and Methods: 556 serum samples comprising 171 patients classified as RA according to the 1987 ACR criteria, 60 patients with other rheumatic diseases and 325 non-rheumatic controls were tested for IgG RF, IgM RF and anti-CCP by ELISA. The findings were then tested in a larger RA case-control cohort (n = 1844). Results: IgG RF predominated over IgM RF in all the investigated ethnic groups. The sensitivity, specificity, and diagnostic accuracy of IgG RF (55.6%, 91.2% and 80.2%, respectively) were superior compared to IgM RF, but comparable to anti-CCP. IgG RF was however, also increased in the Malaysian controls, but the IgG RF superiority over IgM RF was still apparent after cutoff adjustment according to the 1987 ACR criteria. Autoantibody levels did not differ between the three ethnic groups. The Receiver Operating Characteristics (ROC) curves showed larger areas under the curves for IgG RF (0.826) and for anti-CCP (0.867) than for IgM RF (0.737). Review of the literature showed consistently higher sensitivity for IgG RF in studies of Asian RA patients as compared to Caucasian and African-American studies. Conclusion: Increased frequency of IgG RF-positive in RA populations with different genetic background living in Malaysia argues for an environmental factor selectively amplifying the IgG RF response.

In Malaysian and certain Asian countries, snail has high market demand and popular to the local people as food. However, snail is also frequently reported as one of the worst food allergens, dominated by severe symptoms such as asthma and anaphylactic shock. Thus, the aims of this study is to determine the allergenicity of two species of edible snails; the local sea snail, Cerithidea obtusa and the freshwater snail Pomacea canaliculata. Snail extracts were prepared from the snail flesh and analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to determine their protein profiling. Allergenic proteins were detected by immunoblotting test using sera from 10 snail-allergic patients. The snails contain 31 to 34 protein fractions between 11 to >250 kDa. The prominent bands were seen at 33, 42, 74 and 250 kDa. Immunoblotting detected 15 and 16 allergenic proteins in C. obtusa and P. canaliculata, respectively. Three protein fractions at 30, 33 and 42 kDa were identified as the major allergens of C. obtusa, while six major allergens at 30, 33, 42, 74, 124 and 218 kDa were detected in P. canaliculata. Various minor allergens were also detected in both snails. This study indicated that numerous proteins of C. obtusa and P. canaliculata were allergenic. Thus, combined allergen extracts of both snails are essential to be included in diagnosis of snail allergy among local allergic patients.

Objectives Lung exposures including cigarette smoking and silica exposure are associated with the risk of rheumatoid arthritis (RA). We investigated the association between textile dust exposure and the risk of RA in the Malaysian population, with a focus on women who rarely smoke. Methods Data from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) population-based case-control study involving 910 female early RA cases and 910 female age-matched controls were analysed. Self-reported information on ever/never occupationally exposed to textile dust was used to estimate the risk of developing anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA. Interaction between textile dust and the HLA-DRB1 shared epitope (SE) was evaluated by calculating the attributable proportion due to interaction (AP), with 95% CI. Results Occupational exposure to textile dust was significantly associated with an increased risk of developing RA in the Malaysian female population (OR 2.8, 95% CI: 1.6–5.2). The association between occupational exposure to textile dust and risk of RA was uniformly observed for the ACPA-positive RA (OR 2.5, 95% CI: 1.3–4.8) and ACPA-negative RA (OR 3.5, 95% CI: 1.7–7.0) subsets, respectively. We observed a significant interaction between exposure to occupational textile dust and HLA-DRB1 SE alleles regarding the risk of ACPA-positive RA (OR for double exposed: 39.1, 95% CI: 5.1–297.5; AP: 0.8, 95% CI: 0.5–1.2). Conclusions This is the first study demonstrating that textile dust exposure is associated with an increased risk for RA. In addition a gene-environment interaction between HLA-DRB1 SE and textile dust exposure provides a high risk for ACPA-positive RA.

On December 21, 2010, 6000 genetically modified (GM) mosquitoes were released in an uninhabited forest in Malaysia. The purpose of the deliberate release was a limited “marked release and recapture” (MRR) experiment, a standard ecological method in entomology, to evaluate under field conditions, the flight distance and longevity of the sterile male Aedes aegypti strain OX513A(My1), a GM strain. As with any other GM technologies, the release was received with mixed responses. As the scientific community debate over the public engagement strategies for similar GM releases, dengue incidence continues to rise with a heavy toll on morbidity, mortality and healthcare budgets. Meanwhile the wild female Aedes aegypti continues to breed offspring, surviving and evading conventional interventions for vector control.

To characterize the major allergens of Macrobrachium rosenbergii (giant freshwater prawn).Raw and cooked extracts of the giant freshwater prawn were prepared. The IgE reactivity pattern was identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting technique with the sera of 20 skin prick test (SPT) positive patients. The major allergen identified was then characterized using the proteomics approach involving a combination of two-dimensional (2-DE) electrophoresis, mass spectrometry and bioinformatics tools.SDS-PAGE of the raw extract showed 23 protein bands (15-250 kDa) but those ranging from 40 to 100 kDa were not found in the cooked extract. From immunoblotting experiments, raw and cooked extracts demonstrated 11 and 5 IgE-binding proteins, respectively, with a molecular mass ranging from 15 to 155 kDa. A heat-resistant 36 kDa protein was identified as the major allergen of both extracts. In addition, a 42 kDa heat-sensitive protein was shown to be a major allergen of the raw extract. The 2-DE gel fractionated the prawn proteins to more than 50 different protein spots. Of these, 10 spots showed specific IgE reactivity with patients' sera. Matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis led to identification of 2 important allergens, tropomyosin and arginine kinase.It can be concluded that the availability of such allergens would help in component-based diagnosis and therapy of prawn allergies.

Shellfish has been recognized as one of the leading causes of food allergy in both adults and children in Asia Pacific region. In Malaysia, black tiger prawn (Penaeus monodon) is among the most widely consumed species. Our previous studies have successfully identified several major allergens including a thermostable protein of 36 kDa. Thus the aim of this study was to identify the 36 kDa major allergen by an allergenomic approach. Protein extracts of raw prown were prepared and resolved by 2-dimensional electrophoresis (2-DE). Immunoblotting was then performed using sera from patients with prawn allergy. Selected spot from 2-DE was then excised, digested and analyzed by mass spectrometry. The 2-DE profile of the extract revealed approximately 100 protein spots between pH of ~4 to 10 and the size range between (

We investigated the association between cigarette smoking and the risk of developing rheumatoid arthritis (RA) in the Malaysian population. A total of 1,056 RA patients and 1,416 matched controls aged 18–70 years within a defined area of Peninsular Malaysia were evaluated in a case–control study between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched for sex, age, and residential area. Cases and controls answered a questionnaire on a broad range of issues, including lifestyle factors and smoking habits wherein current and former smoking was classified as ever-smoking. The presence of anti-citrullinated peptide antibodies (ACPA) was determined for cases and controls. We found that ever-smokers had an increased risk of developing ACPA-positive RA [odds ratio (OR) = 4.1, 95% confidence interval (CI) 1.9–9.2] but not ACPA-negative RA (OR = 0.7, 95% CI 0.3–2.0), compared with never-smokers. A significant dose–response relationship between cumulative dose of smoking and risk of ACPA-positive RA was observed (

The incidence of aplastic anemia is reported to be higher in Asia than elsewhere. We studied the frequency of human leukocyte antigen (HLA) DRB1 alleles in aplastic anemia patients from 2 genetically similar aboriginal groups, the Kadazan and the Dusun, and compared them with genetically matched community and hospital controls. HLA-DRB1*15 was significantly higher in the patients compared with controls (p = 0.005), confirming similar findings in Japanese and Caucasian studies. Further testing indicated a significantly higher frequency of HLA-DRB1*1501 in patients compared with controls (p = 0.0004) but no significant difference in the frequency of HLA-DRB1*1502. The high frequency of HLA-DRB1*15 in the Kadazan and Dusun population combined with the wide variety of environmental factors associated with aplastic anemia could be the reason for the elevated incidence of aplastic anemia in the Kadazan and Dusun in Sabah.

Background Carbamazepine (CBZ), a frequently used anticonvulsant drug, is one of the most common causes of life-threatening cutaneous adverse drug reactions such as toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS). Recent studies have revealed a strong association between HLA-B*1502 and CBZ-induced TEN/SJS in the Taiwan Han Chinese population. Objectives This study is aimed to investigate the association between human leucocyte antigens (HLA) and CBZ-induced TEN/SJS in the multi-ethnic Malaysian population. Methods A sample of 21 unrelated patients with CBZ-induced TEN/SJS and 300 race-matched, healthy controls were genotyped for HLA-A, -B and -DR using polymerase chain reaction (PCR). Allele frequencies were compared. Results HLA-B*1502 was present in 75.0% (12/16) of Malay patients with CBZ-induced TEN/SJS but in only 15.7% (47/300) of normal controls (odds ratio 16.15, 95% confidence interval 4.57–62.4; corrected P-value = 7.87 × 10−6), which suggests a strong association between HLA and CBZ-induced TEN/SJS. Additionally, HLA-B*1502 was found in all three Chinese and two Indian patients. Existing data show that frequencies of the HLA-B*1502 allele are generally much higher in Asian populations than in White European populations, which explains the higher incidences of SJS and TEN in Asian countries. Conclusions HLA-B*1502 is strongly associated with CBZ-induced TEN/SJS in the Malay population in Malaysia, as has been seen in Han Chinese in Taiwan. This indicates that the genetic association apparent in the incidence of CBZ-induced TEN/SJS is linked with the presence of HLA-B*1502, irrespective of racial origin. Screening of patients for this genetic marker can help to prevent the occurrence of TEN/SJS.

Twenty compounds isolated from Calophyllum inophyllum L., C. inophylloides King, Garcinia opaca King, G. bancana Miq., and G. parvifolia Miq. (Guttiferae) were evaluated for their ability to inhibit platelet aggregation in human whole blood induced by arachidonic acid (AA), collagen, and adenosine diphosphate (ADP). The compounds inhibited platelet aggregation in a dose-dependent manner. Among the compounds tested, 2-(3-methylbut-2-enyl)-1,3,5-trihydroxyxanthone and 2-(3-methylbut-2-enyl)-1,3,5,6- tetrahydroxyxanthone showed strong inhibitory activity on platelet aggregation induced by AA with IC50 values of 115.9 and 113.0 μM, respectively. Rubraxanthone showed inhibitory activity against aggregation caused by the three inducers, and was the most effective antiplatelet compound against collagen-induced platelet aggregation with an IC50 value of 47.0 μM. Macluraxanthone, GB-1a, pyranoamentoflavone, and a neoflavonoid showed selective inhibitory activity on platelet aggregation induced by ADP.

Casticin (1), a flavonoid isolated from the aerial parts of Vitex agnus-castus, was found to be a potent immunomodulatory and cytotoxic compound. The activity was tested in vitro for chemiluminescence, chemotaxis, T-cell proliferation and cytotoxicity. Casticin (1) exhibited a significant inhibitory effect on monocyte oxidative burst in a dose dependent manner. It was found to have a significant suppressive effect on the chemotaxic action at higher concentrations on fMLP (10−8m) stimulated neutrophils. It also showed a potent suppressive effect on PHA stimulated T-cell (PMBC). Copyright © 2009 John Wiley & Sons, Ltd.

Background Many types of shellfish including oysters are sometime cooked before ingestion and it has been demonstrated that cooking may affect the allergenicity of food. Therefore, the aim of our present study is to identify major and minor allergens of tropical oyster (Crassostrea belcheri) and to investigate the effect of different cooking processing on the allergenicity of this oyster. Methods Raw, boiled, fried and roasted extracts of oyster were prepared. Protein profiles were analysed using sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE). Major and minor allergens and allergenicity patterns of all extracts were then determined by immunoblotting with sera from patients with positive skin prick tests (SPT) to the raw oyster extract. Mass-spectrometry was used to identify the major allergenic proteins of this oyster. Results SDS-PAGE of the raw extract showed 15 protein bands (20–180 kDa). In contrast, smaller numbers of protein bands were demonstrated in the boiled extract, those ranging between 40–42 and 55–150 kDa were denatured, whereas the protein profiles were altered to a similar degree by frying or roasting. The 37 kDa proteins had the highest frequency of IgE-binding (95 %), thus identified as the major allergen of this tropical oyster. Other minor IgE-binding proteins were observed at various molecular weights. Immunoblot of raw extract yielded 11 IgE-binding proteins. The cooked extracts showed only a single IgE-binding protein at 37 kDa. Mass spectrometry analysis of the 37 kDa major allergen identified this spot as tropomyosin. Conclusions Cooked extracts produce lower IgE-binding than raw extract, which suggest that thermal treatment can be used as a tool in attempting to reduce oyster allergenicity by reducing the number of IgE-reactive bands. The degree of allergenicity of this oyster was demonstrated in the order raw > boiled > fried ≈ roasted. A heat-resistent 37 kDa protein, corresponding to tropomyosin, was identified as the major allergen of this tropical oyster.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of workplace interventions aimed at treating work‐related rhinitis and rhinosinusitis. We will combine findings of rhinitis and rhinosinusitis in this review due to their similarity in definition, presentation and reported effects but will separate the two entities if possible in our subgroup analysis.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of interventions aimed at preventing the onset of WRR and WRRS in occupational settings. We will combine findings of rhinitis and rhinosinusitis in this review due to their similarity in definition, presentation and reported effects, but we will separate the two entities if possible in our subgroup analysis.

ObjectivesLung exposures including cigarette smoking and silica exposure are associated with the risk of rheumatoid arthritis (RA). We investigated the association between textile dust exposure and the risk of RA in the Malaysian population, with a focus on women who rarely smoke.MethodsData from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis population-based case–control study involving 910 female early RA cases and 910 female age-matched controls were analysed. Self-reported information on ever/never occupationally exposed to textile dust was used to estimate the risk of developing anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA. Interaction between textile dust and the human leucocyte antigen DR β-1 (HLA-DRB1) shared epitope (SE) was evaluated by calculating the attributable proportion due to interaction (AP), with 95% CI.ResultsOccupational exposure to textile dust was significantly associated with an increased risk of developing RA in the Malaysian female population (OR 2.8, 95% CI 1.6 to 5.2). The association between occupational exposure to textile dust and risk of RA was uniformly observed for the ACPA-positive RA (OR 2.5, 95% CI 1.3 to 4.8) and ACPA-negative RA (OR 3.5, 95% CI 1.7 to 7.0) subsets, respectively. We observed a significant interaction between exposure to occupational textile dust and HLA-DRB1 SE alleles regarding the risk of ACPA-positive RA (OR for double exposed: 39.1, 95% CI 5.1 to 297.5; AP: 0.8, 95% CI 0.5 to 1.2).ConclusionsThis is the first study demonstrating that textile dust exposure is associated with an increased risk for RA. In addition, a gene–environment interaction between HLA-DRB1 SE and textile dust exposure provides a high risk for ACPA-positive RA.

Supplemental Digital Content is available in the text, Survivin is a biomarker of cancer known for its anti-apoptotic and cell-cycle regulating properties. In the context of non-cancer pathology, high levels of survivin may be measured in blood and synovial fluid of patients with rheumatoid arthritis (RA) and associate with early joint damage and poor therapy response. The aim of the study was to investigate the value of survivin measurements in blood for diagnosis of RA in the frame of the Malaysian epidemiological investigation of rheumatoid arthritis (MyEIRA) study. The study enrolled RA patients from eight rheumatology centres in Peninsular Malaysia. The healthy controls matched by age, gender and ethnicity were recruited on the community basis from the residential area of the patients. Levels of survivin were measured in blood of RA patients (n = 1233) and controls (n = 1566) by an enzyme-linked immuno-sorbent assay (ELISA). The risk for RA was calculated as odds ratio (OR) and 95% confidence intervals in the individuals with high levels of survivin. The risk was calculated in relation to antibodies against cyclic citrullinated peptides (ACPA), detected by ELISA and HLA-DRB1 shared epitope (SE) alleles, identified by the polymerase chain reaction using sequence specific oligonucleotide method. High levels of survivin were detected in 625 of 1233 (50.7%) RA cases and in 85 of 1566 (5.4%) controls, indicating its high specificity for RA. Survivin was association with an increase in RA risk in the patients having neither SE-alleles nor ACPA (OR = 5.40, 95% CI 3.81–7.66). For the patients combining survivin, SE, and ACPA, the estimated risk for RA was 16-folds higher compared to the survivin negative patients with SE and ACPA(OR = 16.21, 95% CI 5.70–46.18). To conclude, detection of survivin in blood provides a simple test to improve diagnostic and to increase predictability for RA.

Background: Whilst the consumption of bivalves is reasonably high in Malaysia, the frequency of allergy to this group of shellfish in the local population is largely unknown. The aim of this preliminary study was to produce bivalve allergen extracts and to investigate the frequency of bivalve sensitization among the local atopic population. Methods: Raw allergen extracts were prepared from 5 different species of bivalves. Their protein profiles were studied using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Results: In SDS-PAGE, the bivalve extracts demonstrated 10 to 23 protein bands. The five protein profiles varied considerably but most visible protein bands lay within 25-100 kDa. At the same time, fifty patients with a history of atopy were skin prick tested (SPT) with these raw extracts of bivalves. Of the 50 subjects, 13 (26%) had a positive SPT to at least one of the 5 bivalve extracts tested, 8 (61%) reacted to one bivalve extract while only one (8%) reacted to all 5 bivalve extracts. The frequency of skin test reactivity to Malaysian cockle was the highest at 22%, followed by Carpet clam, 12% and 4% to the other 3 bivalve extracts; Tropical oyster, Asian clam and Asian green mussel. Conclusion: This study showed that of the five different bivalve species, cockle was found to have the highest frequency in skin test reactivity. It appears that an individual, who is sensitized to a mite, is also likely to be sensitized to bivalves.

Withanolide, coagulin-H (1), was evaluated for its effect on various cellular functions related to immune response including lymphocyte proliferation, and expression of interleukin-2 (IL-2) cytokine, and results were compared with prednisolone (2), a commonly used immune modulating drug. Coagulin-H (1) was found to have a powerful inhibitory effect on lymphocyte proliferation and Th-1 cytokine production. Inhibition of the phytohaemagglutinin (PHA)-activated T-cell proliferation by coagulin-H (1) was observed in a concentration dependent manner. A complete suppression of PHA-activated T-cell was observed at > or =2.5 microg/mL concentrations of compound (1) and this suppression activity was similar to that of prednisolone (2). Coagulin-H (1) also significantly inhibited IL-2 production by 80%. The interactions of coagulin-H (1) (a natural inhibitor) and prednisolone (2) (a drug) to IL-2 were also investigated in order to understand the differences in their effects on T-cell responses. This paper also describes the results of molecular docking study on IL-2 inhibition. Docking studies predicted that coagulin-H (1) binds to receptor binding site of IL-2 more effectively than prednisolone (2). Based on the computational and the experimental results, coagulin-H (1) was identified as a potential immunosuppressive candidate.