Displaying all 13 publications

  1. Ishak IH, Riveron JM, Ibrahim SS, Stott R, Longbottom J, Irving H, et al.
    Sci Rep, 2016 Apr 20;6:24707.
    PMID: 27094778 DOI: 10.1038/srep24707
    Control of Aedes albopictus, major dengue and chikungunya vector, is threatened by growing cases of insecticide resistance. The mechanisms driving this resistance remain poorly characterised. This study investigated the molecular basis of insecticide resistance in Malaysian populations of Ae. albopictus. Microarray-based transcription profiling revealed that metabolic resistance (cytochrome P450 up-regulation) and possibly a reduced penetration mechanism (consistent over-expression of cuticular protein genes) were associated with pyrethroid resistance. CYP6P12 over-expression was strongly associated with pyrethroid resistance whereas CYP6N3 was rather consistently over-expressed across carbamate and DDT resistant populations. Other detoxification genes also up-regulated in permethrin resistant mosquitoes included a glucuronosyltransferase (AAEL014279-RA) and the glutathione-S transferases GSTS1 and GSTT3. Functional analyses further supported that CYP6P12 contributes to pyrethroid resistance in Ae. albopictus as transgenic expression of CYP6P12 in Drosophila was sufficient to confer pyrethroid resistance in these flies. Furthermore, molecular docking simulations predicted CYP6P12 possessing enzymatic activity towards pyrethroids. Patterns of polymorphism suggested early sign of selection acting on CYP6P12 but not on CYP6N3. The major role played by P450 in the absence of kdr mutations suggests that addition of the synergist PBO to pyrethroids could improve the efficacy of this insecticide class and overcome resistance in field populations of Ae. albopictus.
  2. Ishak IH, Jaal Z, Ranson H, Wondji CS
    Parasit Vectors, 2015;8:181.
    PMID: 25888775 DOI: 10.1186/s13071-015-0797-2
    Knowledge on the extent, distribution and mechanisms of insecticide resistance is essential for successful insecticide-based dengue control interventions. Here, we report an extensive resistance profiling of the dengue vectors Aedes aegypti and Aedes albopictus across Malaysia and establish the contribution of knockdown resistance mechanism revealing significant contrast between both species.
  3. Ishak IH, Kamgang B, Ibrahim SS, Riveron JM, Irving H, Wondji CS
    PLoS Negl Trop Dis, 2017 01;11(1):e0005302.
    PMID: 28114328 DOI: 10.1371/journal.pntd.0005302
    BACKGROUND: Dengue control and prevention rely heavily on insecticide-based interventions. However, insecticide resistance in the dengue vector Aedes aegypti, threatens the continued effectiveness of these tools. The molecular basis of the resistance remains uncharacterised in many endemic countries including Malaysia, preventing the design of evidence-based resistance management. Here, we investigated the underlying molecular basis of multiple insecticide resistance in Ae. aegypti populations across Malaysia detecting the major genes driving the metabolic resistance.

    METHODOLOGY/PRINCIPAL FINDINGS: Genome-wide microarray-based transcription analysis was carried out to detect the genes associated with metabolic resistance in these populations. Comparisons of the susceptible New Orleans strain to three non-exposed multiple insecticide resistant field strains; Penang, Kuala Lumpur and Kota Bharu detected 2605, 1480 and 425 differentially expressed transcripts respectively (fold-change>2 and p-value ≤ 0.05). 204 genes were commonly over-expressed with monooxygenase P450 genes (CYP9J27, CYP6CB1, CYP9J26 and CYP9M4) consistently the most up-regulated detoxification genes in all populations, indicating that they possibly play an important role in the resistance. In addition, glutathione S-transferases, carboxylesterases and other gene families commonly associated with insecticide resistance were also over-expressed. Gene Ontology (GO) enrichment analysis indicated an over-representation of GO terms linked to resistance such as monooxygenases, carboxylesterases, glutathione S-transferases and heme-binding. Polymorphism analysis of CYP9J27 sequences revealed a high level of polymorphism (except in Joho Bharu), suggesting a limited directional selection on this gene. In silico analysis of CYP9J27 activity through modelling and docking simulations suggested that this gene is involved in the multiple resistance in Malaysian populations as it is predicted to metabolise pyrethroids, DDT and bendiocarb.

    CONCLUSION/SIGNIFICANCE: The predominant over-expression of cytochrome P450s suggests that synergist-based (PBO) control tools could be utilised to improve control of this major dengue vector across Malaysia.

  4. Riveron JM, Ibrahim SS, Mulamba C, Djouaka R, Irving H, Wondji MJ, et al.
    G3 (Bethesda), 2017 06 07;7(6):1819-1832.
    PMID: 28428243 DOI: 10.1534/g3.117.040147
    Pyrethroid resistance in malaria vector, An. funestus is increasingly reported across Africa, threatening the sustainability of pyrethroid-based control interventions, including long lasting insecticidal nets (LLINs). Managing this problem requires understanding of the molecular basis of the resistance from different regions of the continent, to establish whether it is being driven by a single or independent selective events. Here, using a genome-wide transcription profiling of pyrethroid resistant populations from southern (Malawi), East (Uganda), and West Africa (Benin), we investigated the molecular basis of resistance, revealing strong differences between the different African regions. The duplicated cytochrome P450 genes (CYP6P9a and CYP6P9b) which were highly overexpressed in southern Africa are not the most upregulated in other regions, where other genes are more overexpressed, including GSTe2 in West (Benin) and CYP9K1 in East (Uganda). The lack of directional selection on both CYP6P9a and CYP6P9b in Uganda in contrast to southern Africa further supports the limited role of these genes outside southern Africa. However, other genes such as the P450 CYP9J11 are commonly overexpressed in all countries across Africa. Here, CYP9J11 is functionally characterized and shown to confer resistance to pyrethroids and moderate cross-resistance to carbamates (bendiocarb). The consistent overexpression of GSTe2 in Benin is coupled with a role of allelic variation at this gene as GAL4-UAS transgenic expression in Drosophila flies showed that the resistant 119F allele is highly efficient in conferring both DDT and permethrin resistance than the L119. The heterogeneity in the molecular basis of resistance and cross-resistance to insecticides in An. funestus populations throughout sub-Saharan African should be taken into account in designing resistance management strategies.
  5. Ishak IH, Low WY, Othman S
    J Sex Med, 2010 Sep;7(9):3080-7.
    PMID: 20584130 DOI: 10.1111/j.1743-6109.2010.01848.x
    INTRODUCTION: Female sexual dysfunction (FSD) is a highly prevalent sexual health problem but poorly investigated at the primary care level.
    AIM: This article examines the prevalence of sexual dysfunction and its possible risk factors associated with women at high risk of FSD in a hospital-based primary practice.
    METHODS: A validated Malay version of the Female Sexual Function Index (MVFSFI) was utilized to determine FSD in a cross-sectional study design, involving 163 married women, aged 18-65 years, in a tertiary hospital-based primary care clinic in Kuala Lumpur, Malaysia. Sociodemographic, marital profile, health, and lifestyle for women at high risk of FSD and those who were not at high risk were compared and their risk factors were determined.
    MAIN OUTCOME MEASURES: Prevalence of FSD in Malaysian women based on the MVFSFI, and its risk factors for developing FSD.
    RESULTS: Some 42 (25.8%) out of 163 women had sexual dysfunction. Prevalence of sexual dysfunction increased significantly with age. Sexual dysfunctions were detected as desire problem (39.3%), arousal problem (25.8%), lubrication problem (21.5%), orgasm problem (16.6%), satisfaction problem (21.5%) and pain problems (16.6%). Women at high risk of FSD were significantly associated with age (OR 4.1, 95% CI 1.9 to 9.0), husband's age (OR 4.3 95% C.I 1.9 to 9.3), duration of marriage (OR 3.3, 95% CI 1.6 to 6.8), medical problems (OR 8.5, 95% CI 3.3 to 21.7), menopausal status (OR 6.6, 95% CI 3.1 to 14.3), and frequency of sexual intercourse (OR 10.7, 95% CI 3.6 to 31.7). Multivariate analysis showed that medical problem (adjusted OR 4.6, 95% CI 1.6 to 14.0) and frequency of sexual intercourse (adjusted OR 7.2, 95% CI 2.1 to 24.0) were associated with increased risk of having FSD. Those who practiced contraception were less likely to have FSD.
    CONCLUSION: Sexual health problems are prevalent in women attending primary care clinic where one in four women were at high risk of FSD. Thus, primary care physician should be trained and prepared to address this issue.
    Study site: Primary Care Clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  6. Vanoh D, Ishak IH, Shahar S, Manaf ZA, Ali NM, Noah SAM
    Clin Interv Aging, 2018;13:1787-1798.
    PMID: 30271134 DOI: 10.2147/CIA.S157324
    Background: The increase in the population of aging people has increased the occurrence of cognitive decline leading to predemented stage of dementia, ie, mild cognitive impairment (MCI). The cognitive tools that are web-based have been proven to be useful in decreasing the risk of MCI. Thus, in the present study, an education tool that is web-based, called WESIHAT 2.0©, had been created to educate elderly people about precautionary strategies against MCI.

    Methodology: WESIHAT 2.0 was devised in a senior-friendly style, which includes touch screen, greater font size, larger icons, and employed multimedia components of text, images, and videos. The components employed in WESIHAT 2.0 were a screening tool called TUA-WELLNESS, 10 guides for memory improvement, health diary, and guide for a healthy menu. This application assessed a group of 73 candidates consisting of elderly people, health professionals, caregivers, and information technology (IT) professionals for 1 month.

    Results: All the elderly people, caregivers, and 75% of IT and health professionals were satisfied with the subject matter of WESIHAT 2.0. About more than half of the elderly people, caregivers, and IT and health professionals had given a consensus on the comprehensive ease of the terminologies, sentences, images, table, and advice related to diet included in the web application. Proposals for improvements of the web portal included suggestions such as using smaller sentences, using greater font size, adding more images, and avoiding the use of unfamiliar terminologies.

    Conclusion: WESIHAT 2.0 is a suitable tool for educating older people about the lifestyle modification strategies to slower progression to cognitive impairment, with regard to the significance of expert advice.

  7. Husna Zulkrnin NS, Rozhan NN, Zulkfili NA, Nik Yusoff NR, Rasat MSM, Abdullah NH, et al.
    J Parasitol Res, 2018;2018:1383186.
    PMID: 30050688 DOI: 10.1155/2018/1383186
    Dengue is vector-borne diseases with 390 million infections per year extending over 120 countries of the world. Aedes aegypti (L.) (Diptera: Culicidae) is a primary vector for dengue viral infections for humans. Current focus on application of natural product against mosquito vectors has been the main priority for research due to its eco-safety. The extensive use of chemical insecticides has led to severe health problems, environmental pollution, toxic hazards to human and nontarget species, and development of insecticide resistance on mosquitoes. Azolla pinnata is an aquatic fern and predominantly used as feed in poultry industry and as fertilizer in agricultural field for enhancing the fertility of rice paddy soil. The present study was conducted to explore the larvicidal efficacy of A. pinnata using fresh and powdered form against late third-stage larvae (6 days, 5 mm in larvae body length) of Ae. aegypti (L.) (Diptera: Culicidae). The larvicidal bioassays were performed using World Health Organization standard larval susceptibility test method for different concentration for powdered and fresh A. pinnata. Powdered A. pinnata concentration used during larvicidal bioassay ranges from 500ppm to 2000ppm; meanwhile, fresh A. pinnata ranges from 500ppm to 9,000,000 ppm. The highest mortality was at 1853 ppm for powdered A. pinnata compared with fresh A. pinnata at 2,521,535 ppm, while the LC50 for both powdered and fresh A. pinnata recorded at 1262 ppm and 1853 ppm, respectively. Finally, the analysis of variance (ANOVA) showed significant difference on Ae. aegypti larval mortality (F=30.439, df=1, p≤0.001) and concentration (F=20.002, df=1, p≤0.001) compared to powdered and fresh A. pinnata at 24-hour bioassay test. In conclusion, the powdered A. pinnata serves as a good larvicidal agent against Ae. aegypti (L.) (Diptera: Culicidae) and this study provided information on the lethal concentration that may have potential for a more eco-friendly Aedes mosquito control program.
  8. Rahim J, Ahmad AH, Kassim NF, Ahmad H, Ishak IH, Rus AC, et al.
    J. Am. Mosq. Control Assoc., 2016 Sep;32(3):210-216.
    PMID: 27802400
    Dengue vector control still heavily relies on the use of chemical insecticides, and the widespread use of insecticides has led to resistance in mosquitoes. The diagnostic dose is a key part of resistance monitoring. The present study corroborates the discriminating lethal doses of temephos and malathion based on dose-response of known susceptible strain of Aedes albopictus following the World Health Organization (WHO) diagnostic test procedure. Late 3rd and early 4th instars were tested with a range of larvicides to determine the lethal concentrations (LC50 and LC99) values. A slightly higher diagnostic dose of 0.020 mg/liter as compared with the WHO-established value of 0.012 mg/liter was observed for temephos. Meanwhile, a malathion diagnostic dose of 0.200 mg/liter is also reported here since there are no such reported values by WHO. Doubling the LC99 values of susceptible strains, 3 of the 5 wild-collected populations showed resistance to temephos and 2 showed incipient resistance; all 5 populations showed incipient resistance to malathion. The revised and established lethal diagnostic dose findings from the current work are crucial to elaborate on the variation in susceptibility of Ae. albopictus in future resistance monitoring programs in Malaysia.
  9. Rahim J, Ahmad AH, Ahmad H, Ishak IH, Rus AC, Maimusa HA
    J. Am. Mosq. Control Assoc., 2017 Sep;33(3):200-208.
    PMID: 28854111 DOI: 10.2987/16-6607R.1
    Insecticide-based vector control approaches are facing challenges due to the development of resistance in vector mosquitoes. Therefore, a proper resistance surveillance program using baseline lethal concentrations is crucial for resistance management strategies. Currently, the World Health Organization's (WHO) diagnostic doses established for Aedes aegypti and Anopheles species are being used to study the resistance status of Aedes albopictus. In this study, we established the diagnostic doses for permethrin, deltamethrin, and malathion using a known susceptible reference strain. Five field-collected populations were screened against these doses, following the WHO protocol. This study established the diagnostic dose of malathion at 2.4%, permethrin at 0.95%, and deltamethrin at 0.28%, which differ from the WHO doses for Aedes aegypti and Anopheles spp. Among the insecticides tested on the 5 wild populations, only deltamethrin showed high effectiveness. Different susceptibility and resistance patterns were observed with permethrin, malathion, and dichloro-diphenyl-trichloroethane (DDT) at 4%. This study may assist the health authorities to improve future chemical-based vector control operations in dengue-endemic areas.
  10. Sherpa S, Guéguen M, Renaud J, Blum MGB, Gaude T, Laporte F, et al.
    Ecol Evol, 2019 Nov;9(22):12658-12675.
    PMID: 31788205 DOI: 10.1002/ece3.5734
    Invasive species can encounter environments different from their source populations, which may trigger rapid adaptive changes after introduction (niche shift hypothesis). To test this hypothesis, we investigated whether postintroduction evolution is correlated with contrasting environmental conditions between the European invasive and source ranges in the Asian tiger mosquito Aedes albopictus. The comparison of environmental niches occupied in European and source population ranges revealed more than 96% overlap between invasive and source niches, supporting niche conservatism. However, we found evidence for postintroduction genetic evolution by reanalyzing a published ddRADseq genomic dataset from 90 European invasive populations using genotype-environment association (GEA) methods and generalized dissimilarity modeling (GDM). Three loci, among which a putative heat-shock protein, exhibited significant allelic turnover along the gradient of winter precipitation that could be associated with ongoing range expansion. Wing morphometric traits weakly correlated with environmental gradients within Europe, but wing size differed between invasive and source populations located in different climatic areas. Niche similarities between source and invasive ranges might have facilitated the establishment of populations. Nonetheless, we found evidence for environmental-induced adaptive changes after introduction. The ability to rapidly evolve observed in invasive populations (genetic shift) together with a large proportion of unfilled potential suitable areas (80%) pave the way to further spread of Ae. albopictus in Europe.
  11. Dzaki N, Ramli KN, Azlan A, Ishak IH, Azzam G
    Sci Rep, 2017 03 16;7:43618.
    PMID: 28300076 DOI: 10.1038/srep43618
    The mosquito Aedes aegypti (Ae. aegypti) is the most notorious vector of illness-causing viruses such as Dengue, Chikugunya, and Zika. Although numerous genetic expression studies utilizing quantitative real-time PCR (qPCR) have been conducted with regards to Ae. aegypti, a panel of genes to be used suitably as references for the purpose of expression-level normalization within this epidemiologically important insect is presently lacking. Here, the usability of seven widely-utilized reference genes i.e. actin (ACT), eukaryotic elongation factor 1 alpha (eEF1α), alpha tubulin (α-tubulin), ribosomal proteins L8, L32 and S17 (RPL8, RPL32 and RPS17), and glyceraldeyde 3-phosphate dehydrogenase (GAPDH) were investigated. Expression patterns of the reference genes were observed in sixteen pre-determined developmental stages and in cell culture. Gene stability was inferred from qPCR data through three freely available algorithms i.e. BestKeeper, geNorm, and NormFinder. The consensus rankings generated from stability values provided by these programs suggest a combination of at least two genes for normalization. ACT and RPS17 are the most dependably expressed reference genes and therefore, we propose an ACT/RPS17 combination for normalization in all Ae. aegypti derived samples. GAPDH performed least desirably, and is thus not a recommended reference gene. This study emphasizes the importance of validating reference genes in Ae. aegypti for qPCR based research.
  12. Mohamad Nor NS, Ambak R, Mohd Zaki N, Abdul Aziz NS, Cheong SM, Abd Razak MA, et al.
    BMC Womens Health, 2018 07 19;18(Suppl 1):114.
    PMID: 30066661 DOI: 10.1186/s12905-018-0590-4
    BACKGROUND: Obesity is a global health burden in the non-communicable diseases and much efforts have been implemented in the past decade in response to the rise of obesity prevalence among the Malaysian population. These include the development of the national policies, health programmes and research activities. The main aim of the scoping review was to identify obesity research pattern among adults in Malaysia in terms of the scopes, topics and the research designs.

    METHODS: The scoping review was conducted based on the framework by Arksey and O'Malley. The Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) diagram was used as a guide to record the review process. Articles from year 2008 until 2017 on overweight and obesity among adults aged 18 years and above were retrieved based on the keywords using electronic databases (Embase/Ovid, Pubmed, Cochrane library and Google Scholar). Local journals, Nutrition Research in Malaysia Biblography (2011 and 2016), online local theses databases, virtual library databases were also included in the searches. Consultations with relevant key informants from the National Institutes of Health and local universities were also conducted. Search activities were managed using Endnote software and MS Excelsheet.

    RESULTS: The characteristics of the results were described based on the objectives of the review. A total of 2004 articles and reports were retrieved, and 188 articles related to obesity in Malaysia were included in the final review. Scopes and topics of obesity research based on the Nutrition Research Priorities in Malaysia (NRPM) for 11th Malaysia Plan were obesity prevalence, weight loss intervention, association of physical activities and dietary factors with obesity. The majority of obesity research among adults in Malaysia was cross sectional studies and only a small number of intervention studies, qualitative studies and systematic review were indentified. Research gaps were identified in order to make useful recommendations to the stakeholders.

    CONCLUSIONS: In the past decade, there has been an emerging evidence on obesity research among adults in Malaysia. More obesity research needs to be conducted particularly on obesity intervention among specific gender, qualitative studies, economic cost and genetic factors of obesity.

  13. Ravi R, Zulkrnin NSH, Rozhan NN, Nik Yusoff NR, Mat Rasat MS, Ahmad MI, et al.
    PLoS ONE, 2018;13(11):e0206982.
    PMID: 30399167 DOI: 10.1371/journal.pone.0206982
    BACKGROUND: The resistance problem of dengue vectors to different classes of insecticides that are used for public health has raised concerns about vector control programmes. Hence, the discovery of alternative compounds that would enhance existing tools is important for overcoming the resistance problem of using insecticides in vectors and ensuring a chemical-free environment. The larvicidal effects of Azolla pinnata extracts by using two different extraction methods with methanol solvent against Aedes in early 4th instar larvae was conducted.

    METHODS: The fresh Azolla pinnata plant from Kuala Krai, Kelantan, Malaysia was used for crude extraction using Soxhlet and maceration methods. Then, the chemical composition of extracts and its structure were identified using GCMS-QP2010 Ultra (Shimadzu). Next, following the WHO procedures for larval bioassays, the extracts were used to evaluate the early 4th instar larvae of Aedes mosquito vectors.

    RESULTS: The larvicidal activity of Azolla pinnata plant extracts evidently affected the early 4th instar larvae of Aedes aegypti mosquito vectors. The Soxhlet extraction method had the highest larvicidal effect against Ae. aegypti early 4th instar larvae, with LC50 and LC95 values of 1093 and 1343 mg/L, respectively. Meanwhile, the maceration extraction compounds were recorded with the LC50 and LC95 values of 1280 and 1520 mg/L, respectively. The larvae bioassay test for Ae. albopictus showed closely similar values in its Soxhlet extraction, with LC50 and LC95 values of 1035 and 1524 mg/L, compared with the maceration extraction LC50 and LC95 values of 1037 and 1579 mg/L, respectively. The non-target organism test on guppy fish, Poecilia reticulata, showed no mortalities and posed no toxic effects. The chemical composition of the Azolla pinnata plant extract has been found and characterized as having 18 active compounds for the Soxhlet method and 15 active compounds for the maceration method.

    CONCLUSIONS: Our findings showed that the crude extract of A. pinnata bioactive molecules are effective and have the potential to be developed as biolarvicides for Aedes mosquito vector control. This study recommends future research on the use of active ingredients isolated from A. pinnata extracts and their evaluation against larvicidal activity of Aedes in small-scale field trials for environmentally safe botanical insecticide invention.

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