Displaying publications 121 - 133 of 133 in total

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  1. Dahalan FA, Sidek HM, Murtey MD, Embi MN, Ibrahim J, Fei Tieng L, et al.
    Biomed Res Int, 2016;2016:1645097.
    PMID: 27525262 DOI: 10.1155/2016/1645097
    Plasmodium falciparum mitogen-activated protein (MAP) kinases, a family of enzymes central to signal transduction processes including inflammatory responses, are a promising target for antimalarial drug development. Our study shows for the first time that the P. falciparum specific MAP kinase 2 (PfMAP2) is colocalized in the nucleus of all of the asexual erythrocytic stages of P. falciparum and is particularly elevated in its phosphorylated form. It was also discovered that PfMAP2 is expressed in its highest quantity during the early trophozoite (ring form) stage and significantly reduced in the mature trophozoite and schizont stages. Although the phosphorylated form of the kinase is always more prevalent, its ratio relative to the nonphosphorylated form remained constant irrespective of the parasites' developmental stage. We have also shown that the TSH motif specifically renders PfMAP2 genetically divergent from the other plasmodial MAP kinase activation sites using Neighbour Joining analysis. Furthermore, TSH motif-specific designed antibody is crucial in determining the location of the expression of the PfMAP2 protein. However, by using immunoelectron microscopy, PPfMAP2 were detected ubiquitously in the parasitized erythrocytes. In summary, PfMAP2 may play a far more important role than previously thought and is a worthy candidate for research as an antimalarial.
    Matched MeSH terms: Malaria, Falciparum/drug therapy
  2. Norahmad NA, Mohd Abd Razak MR, Abdullah NR, Sastu UR, Imwong M, Muniandy PK, et al.
    PLoS One, 2016;11(10):e0165515.
    PMID: 27788228 DOI: 10.1371/journal.pone.0165515
    Chloroquine (CQ) and fansidar (sulphadoxine-pyrimethamine, SP) were widely used for treatment of Plasmodium falciparum for several decades in Malaysia prior to the introduction of Artemisinin-based Combination Therapy (ACT) in 2008. Our previous study in Kalabakan, located in south-east coast of Sabah showed a high prevalence of resistance to CQ and SP, suggesting the use of the treatment may no longer be effective in the area. This study aimed to provide a baseline data of antimalarial drug resistant markers on P. falciparum isolates in Kota Marudu located in the north-east coast of Sabah. Mutations on genes associated with CQ (pfcrt and pfmdr1) and SP (pfdhps and pfdhfr) were assessed by PCR amplification and restriction fragment length polymorphism. Mutations on the kelch13 marker (K13) associated with artemisinin resistance were determined by DNA sequencing technique. The assessment of pfmdr1 copy number variation associated with mefloquine resistant was done by real-time PCR technique. A low prevalence (6.9%) was indicated for both pfcrt K76T and pfmdr1 N86Y mutations. All P. falciparum isolates harboured the pfdhps A437G mutation. Prevalence of pfdhfr gene mutations, S108N and I164L, were 100% and 10.3%, respectively. Combining the different resistant markers, only two isolates were conferred to have CQ and SP treatment failure markers as they contained mutant alleles of pfcrt and pfmdr1 together with quintuple pfdhps/pfdhfr mutation (combination of pfdhps A437G+A581G and pfdhfr C59R+S108N+I164L). All P. falciparum isolates carried single copy number of pfmdr1 and wild type K13 marker. This study has demonstrated a low prevalence of CQ and SP resistance alleles in the study area. Continuous monitoring of antimalarial drug efficacy is warranted and the findings provide information for policy makers in ensuring a proper malaria control.
    Matched MeSH terms: Malaria, Falciparum/drug therapy*
  3. Liew JWK, Mahpot RB, Dzul S, Abdul Razak HAB, Ahmad Shah Azizi NAB, Kamarudin MB, et al.
    Am J Trop Med Hyg, 2018 06;98(6):1709-1713.
    PMID: 29877176 DOI: 10.4269/ajtmh.17-1010
    Although Plasmodium vivax infections in Malaysia are usually imported, a significant autochthonous outbreak of vivax malaria was detected in a remote indigenous (Orang Asli) settlement located in northern peninsular Malaysia. Between November 2016 and April 2017, 164 cases of P. vivax infection were detected. Although 83.5% of the vivax cases were identified through passive case detection and contact screening during the first 7 weeks, subsequent mass blood screening (combination of rapid diagnostic tests, blood films, and polymerase chain reaction [PCR]) of the entire settlement (N = 3,757) revealed another 27 P. vivax infections, 19 of which were asymptomatic. The mapped data from this active case detection program was used to direct control efforts resulting in the successful control of the outbreak in this region. This report highlights the importance of proactive case surveillance and timely management of malaria control in Malaysia as it nears malaria elimination.
    Matched MeSH terms: Malaria, Falciparum/epidemiology*
  4. Al-Mekhlafi HM, Madkhali AM, Ghailan KY, Abdulhaq AA, Ghzwani AH, Zain KA, et al.
    Malar J, 2021 Jul 13;20(1):315.
    PMID: 34256757 DOI: 10.1186/s12936-021-03846-4
    BACKGROUND: Saudi Arabia and Yemen are the only two countries in the Arabian Peninsula that are yet to achieve malaria elimination. Over the past two decades, the malaria control programme in Saudi Arabia has successfully reduced the annual number of malaria cases, with the lowest incidence rate across the country reported in 2014. This study aims to investigate the distribution of residual malaria in Jazan region and to identify potential climatic drivers of autochthonous malaria cases in the region.

    METHODS: A cross-sectional study was carried out from 1 April 2018 to 31 January 2019 in Jazan region, southwestern Saudi Arabia, which targeted febrile individuals attending hospitals and primary healthcare centres. Participants' demographic data were collected, including age, gender, nationality, and residence. Moreover, association of climatic variables with the monthly autochthonous malaria cases reported during the period of 2010-2017 was retrospectively analysed.

    RESULTS: A total of 1124 febrile subjects were found to be positive for malaria during the study period. Among them, 94.3 and 5.7% were infected with Plasmodium falciparum and Plasmodium vivax, respectively. In general, subjects aged 18-30 years and those aged over 50 years had the highest (42.7%) and lowest (5.9%) percentages of malaria cases. Similarly, the percentage of malaria-positive cases was higher among males than females (86.2 vs 13.8%), among non-Saudi compared to Saudi subjects (70.6 vs 29.4%), and among patients residing in rural rather than in urban areas (89.8 vs 10.2%). A total of 407 autochthonous malaria cases were reported in Jazan region between 2010 and 2017. Results of zero-inflated negative binomial regression analysis showed that monthly average temperature and relative humidity were the significant climatic determinants of autochthonous malaria in the region.

    CONCLUSION: Malaria remains a public health problem in most governorates of Jazan region. The identification and monitoring of malaria transmission hotspots and predictors would enable control efforts to be intensified and focused on specific areas and therefore expedite the elimination of residual malaria from the whole region.

    Matched MeSH terms: Malaria, Falciparum/epidemiology*
  5. Chan KL, Choo CY, Abdullah NR
    Planta Med, 2005 Oct;71(10):967-9.
    PMID: 16254833 DOI: 10.1055/s-2005-864188
    Among the quassinoids isolated from Eurycoma longifolia Jack, eurycomanone was identified as the most potent and toxic inhibitor of the chloroquine-resistant Gombak A isolate of Plasmodium falciparum. Several diacylated derivatives of eurycomanone, 1,15-di-O-isovaleryleurycomanone, 1,15-di-O-(3,3-dimethylacryloyl)- eurycomanone and 1,15-di-O-benzoyleurycomanone were synthesized by direct acylation with the respective acid chlorides. The monoacylated 15-O-isovaleryleurycomanone was synthesized by selective protection of the other hydroxy groups of eurycomanone with trimethylsilyl trifluoromethanesulphonate to enable the exclusive acylation of its C-15 hydroxy group. This was followed by the removal of the protecting groups with citric acid. The diacylated eurycomanones exhibited lower antiplasmodial activity against the Gombak A isolates and lower toxicity in the brine shrimp assay when compared to eurycomanone. In contrast, the monoacylated derivative displayed comparable antiplasmodial potency to eurycomanone, but its toxicity was reduced. Thus, preliminary studies of the synthesized acylated eurycomanones have shown that acylation only at the C-15 hydroxy group may be worthy of further antimalarial investigation.
    Matched MeSH terms: Malaria, Falciparum/drug therapy
  6. Jeffree SM, Ahmed K, Safian N, Hassan R, Mihat O, Lukman KA, et al.
    Am J Trop Med Hyg, 2018 Jan;98(1):45-50.
    PMID: 29141714 DOI: 10.4269/ajtmh.17-0081
    Sabah is a Malaysian state situated in the northern part of Borneo, and it is endemic for malaria. The incidence of malaria is the lowest (0.05/1,000 population) in Penampang districts of Sabah. In June 26, 2012, two Plasmodium falciparum malaria cases were notified to public health department from a village in Penampang. Immediate investigation was initiated to identify the risk factors and to institute control measures. We performed active case finding by asking household members of all houses in the village regarding malaria symptoms and by examining blood smears. Environmental investigation was performed by collecting samples to detect mosquito breeding sites and to identify malaria transmitting vector mosquitoes. A case-control study with a ratio of 1:4 (11 cases and 44 controls) was conducted using self-administered questionnaire. The microscopic examination of blood smear for malarial parasite and entomology sampling was carried out. The malarial attack rate was 2.3%, 6/11 smears have gametocyte, and the case fatality rate was 9.1%. One case was a migrant rubber tapper from Indonesia which happened to be the first case with gametocyte positive. Overall, the incidence of malaria was higher (6/11) among rubber tappers. The odds of cases for those living nearby stagnant water were 7.3 [95% confidence interval: 1.2-43.5] times higher. In conclusion, an outbreak of P. falciparum malaria was introduced into a malaria-free village by a migrant rubber tapper, by whom the imported parasite was introduced to the community via vector Anopheles balabacensis. Living near stagnant water bodies was the risk factor in this outbreak.
    Matched MeSH terms: Malaria, Falciparum/epidemiology*
  7. Grigg MJ, William T, Drakeley CJ, Jelip J, von Seidlein L, Barber BE, et al.
    BMJ Open, 2014 Aug 22;4(8):e006004.
    PMID: 25149186 DOI: 10.1136/bmjopen-2014-006004
    INTRODUCTION: Plasmodium knowlesi has long been present in Malaysia, and is now an emerging cause of zoonotic human malaria. Cases have been confirmed throughout South-East Asia where the ranges of its natural macaque hosts and Anopheles leucosphyrus group vectors overlap. The majority of cases are from Eastern Malaysia, with increasing total public health notifications despite a concurrent reduction in Plasmodium falciparum and P. vivax malaria. The public health implications are concerning given P. knowlesi has the highest risk of severe and fatal disease of all Plasmodium spp in Malaysia. Current patterns of risk and disease vary based on vector type and competence, with individual exposure risks related to forest and forest-edge activities still poorly defined. Clustering of cases has not yet been systematically evaluated despite reports of peri-domestic transmission and known vector competence for human-to-human transmission.

    METHODS AND ANALYSIS: A population-based case-control study will be conducted over a 2-year period at two adjacent districts in north-west Sabah, Malaysia. Confirmed malaria cases presenting to the district hospital sites meeting relevant inclusion criteria will be requested to enrol. Three community controls matched to the same village as the case will be selected randomly. Study procedures will include blood sampling and administration of household and individual questionnaires to evaluate potential exposure risks associated with acquisition of P. knowlesi malaria. Secondary outcomes will include differences in exposure variables between P. knowlesi and other Plasmodium spp, risk of severe P. knowlesi malaria, and evaluation of P. knowlesi case clustering. Primary analysis will be per protocol, with adjusted ORs for exposure risks between cases and controls calculated using conditional multiple logistic regression models.

    ETHICS: This study has been approved by the human research ethics committees of Malaysia, the Menzies School of Health Research, Australia, and the London School of Hygiene and Tropical Medicine, UK.

    Matched MeSH terms: Malaria, Falciparum
  8. Al-Mekhlafi AM, Mahdy MA, A Azazy A, Fong MY
    Parasit Vectors, 2010 Nov 19;3:110.
    PMID: 21092097 DOI: 10.1186/1756-3305-3-110
    BACKGROUND: Malaria is an endemic disease in Yemen and is responsible for 4.9 deaths per 100,000 population per year and 43,000 disability adjusted life years lost. Although malaria in Yemen is caused mainly by Plasmodium falciparum and Plasmodium vivax, there are no sequence data available on the two species. This study was conducted to investigate the distribution of the Plasmodium species based on the molecular detection and to study the molecular phylogeny of these parasites.

    METHODS: Blood samples from 511 febrile patients were collected and a partial region of the 18 s ribosomal RNA (18 s rRNA) gene was amplified using nested PCR. From the 86 positive blood samples, 13 Plasmodium falciparum and 4 Plasmodium vivax were selected and underwent cloning and, subsequently, sequencing and the sequences were subjected to phylogenetic analysis using the neighbor-joining and maximum parsimony methods.

    RESULTS: Malaria was detected by PCR in 86 samples (16.8%). The majority of the single infections were caused by P. falciparum (80.3%), followed by P. vivax (5.8%). Mixed infection rates of P. falciparum + P. vivax and P. falciparum + P. malariae were 11.6% and 2.3%, respectively. All P. falciparum isolates were grouped with the strain 3D7, while P. vivax isolates were grouped with the strain Salvador1. Phylogenetic trees based on 18 s rRNA placed the P. falciparum isolates into three sub-clusters and P. vivax into one cluster. Sequence alignment analysis showed 5-14.8% SNP in the partial sequences of the 18 s rRNA of P. falciparum.

    CONCLUSIONS: Although P. falciparum is predominant, P. vivax, P. malariae and mixed infections are more prevalent than has been revealed by microscopy. This overlooked distribution should be considered by malaria control strategy makers. The genetic polymorphisms warrant further investigation.

    Matched MeSH terms: Malaria, Falciparum
  9. Dieye Y, Mbengue B, Dagamajalu S, Fall MM, Loke MF, Nguer CM, et al.
    PeerJ, 2016;4:e1965.
    PMID: 27168977 DOI: 10.7717/peerj.1965
    Background. With 214 million cases and 438,000 deaths in 2015, malaria remains one of the deadliest infectious diseases in tropical countries. Several species of the protozoan Plasmodium cause malaria. However, almost all the fatalities are due to Plasmodium falciparum, a species responsible for the severest cases including cerebral malaria. Immune response to Plasmodium falciparum infection is mediated by the production of pro-inflammatory cytokines, chemokines and growth factors whose actions are crucial for the control of the parasites. Following this response, the induction of anti-inflammatory immune mediators downregulates the inflammation thus preventing its adverse effects such as damages to various organs and death. Methods. We performed a retrospective, nonprobability sampling study using clinical data and sera samples from patients, mainly adults, suffering of non-cerebral or cerebral malaria in Dakar, Sénégal. Healthy individuals residing in the same area were included as controls. We measured the serum levels of 29 biomarkers including growth factors, chemokines, inflammatory and anti-inflammatory cytokines. Results. We found an induction of both pro- and anti-inflammatory immune mediators during malaria. The levels of pro-inflammatory biomarkers were higher in the cerebral malaria than in the non-cerebral malaria patients. In contrast, the concentrations of anti-inflammatory cytokines were comparable in these two groups or lower in CM patients. Additionally, four pro-inflammatory biomarkers were significantly increased in the deceased of cerebral malaria compared to the survivors. Regarding organ damage, kidney failure was significantly associated with death in adults suffering of cerebral malaria. Conclusions. Our results suggest that a poorly controlled inflammatory response determines a bad outcome in African adults suffering of cerebral malaria.
    Matched MeSH terms: Malaria, Falciparum
  10. Mohd Fakharul Zaman Raja Yahya, Hasidah Mohd Sidek
    MyJurnal
    Malaria parasites, Plasmodium can infect a wide range of hosts including humans and rodents. There are two copies of mitogen activated protein kinases (MAPKs) in Plasmodium, namely MAPK1 and MAPK2. The MAPKs have been studied extensively in the human Plasmodium, P. falciparum. However, the MAPKs from other Plasmodium species have not been characterized and it is therefore the premise of presented study to characterize the MAPKs from other Plasmodium species-P. vivax, P knowlesi, P berghei, P chabaudi and P.yoelli using a series of publicly available bioinformatic tools. In silico data indicates that all Plasmodium MAPKs are nuclear-localized and contain both a nuclear localization signal (NLS) and a Leucine-rich nuclear export signal (NES). The activation motifs of TDY and TSH were found to be fully conserved in Plasmodium MAPK1 and MAPK2, respectively. The detailed manual inspection of a multiple sequence alignment (MSA) construct revealed a total of 17 amino acid stack patterns comprising of different amino acids present in MAPK1 and MAPK2 respectively, with respect to rodent and human Plasmodia. It is proposed that these amino acid stack patterns may be useful in explaining the disparity between rodent and human Plasmodium MAPKs.
    Matched MeSH terms: Malaria, Falciparum
  11. Nurul AA, Norazmi MN
    Parasitol Res, 2011 Apr;108(4):887-97.
    PMID: 21057812 DOI: 10.1007/s00436-010-2130-5
    Vaccine development against the blood-stage malaria parasite is aimed at reducing the pathology of the disease. We constructed a recombinant Mycobacterium bovis bacille Calmette Guerin (rBCG) expressing the 19 kDa C-terminus of Plasmodium falciparum merozoite surface protein-1 (MSP-1(19)) to evaluate its protective ability against merozoite invasion of red blood cells in vitro. A mutated version of MSP-1(19), previously shown to induce the production of inhibitory but not blocking antibodies, was cloned into a suitable shuttle plasmid and transformed into BCG Japan (designated rBCG016). A native version of the molecule was also cloned into BCG (rBCG026). Recombinant BCG expressing the mutated version of MSP-1(19) (rBCG016) elicited enhanced specific immune response against the epitope in BALB/c mice as compared to rBCG expressing the native version of the epitope (rBCG026). Sera from rBCG016-immunized mice contained significant levels of specific IgG, especially of the IgG2a subclass, against MSP-1(19) as determined by enzyme-linked immunosorbent assay. The sera was reactive with fixed P. falciparum merozoites as demonstrated by indirect immunofluorescence assay (IFA) and inhibited merozoite invasion of erythrocytes in vitro. Furthermore, lymphocytes from rBCG016-immunized mice demonstrated higher proliferative response against the MSP-1(19) antigen as compared to those of rBCG026- and BCG-immunized animals. rBCG expressing the mutated version of MSP-1(19) of P. falciparum induced enhanced humoral and cellular responses against the parasites paving the way for the rational use of rBCG as a blood-stage malaria vaccine candidate.
    Matched MeSH terms: Malaria, Falciparum/prevention & control*
  12. Jiram AI, Ooi CH, Rubio JM, Hisam S, Karnan G, Sukor NM, et al.
    Malar J, 2019 May 02;18(1):156.
    PMID: 31046769 DOI: 10.1186/s12936-019-2786-y
    BACKGROUND: Malaysia has declared its aim to eliminate malaria with a goal of achieving zero local transmission by the year 2020. However, targeting the human reservoir of infection, including those with asymptomatic infection is required to achieve malaria elimination. Diagnosing asymptomatic malaria is not as straightforward due to the obvious lack of clinical manifestations and often subpatent level of parasites. Accurate diagnosis of malaria is important for providing realistic estimates of malaria burden and preventing misinformed interventions. Low levels of parasitaemia acts as silent reservoir of transmission thus remains infectious to susceptible mosquito vectors. Hence, the aim of this study is to investigate the prevalence of asymptomatic submicroscopic malaria (SMM) in the District of Belaga, Sarawak.

    METHODS: In 2013, a total of 1744 dried blood spots (DBS) were obtained from residents of 8 longhouses who appeared healthy. Subsequently, 251 venous blood samples were collected from residents of 2 localities in 2014 based on the highest number of submicroscopic cases from prior findings. Thin and thick blood films were prepared from blood obtained from all participants in this study. Microscopic examination were carried out on all samples and a nested and nested multiplex PCR were performed on samples collected in 2013 and 2014 respectively.

    RESULTS: No malaria parasites were detected in all the Giemsa-stained blood films. However, of the 1744 samples, 29 (1.7%) were positive for Plasmodium vivax by PCR. Additionally, of the 251 samples, the most prevalent mono-infection detected by PCR was Plasmodium falciparum 50 (20%), followed by P. vivax 39 (16%), P. knowlesi 9 (4%), and mixed infections 20 (8%).

    CONCLUSIONS: This research findings conclude evidence of Plasmodium by PCR, among samples previously undetectable by routine blood film microscopic examination, in local ethnic minority who are clinically healthy. SMM in Belaga district is attributed not only to P. vivax, but also to P. falciparum and P. knowlesi. In complementing efforts of programme managers, there is a need to increase surveillance for SMM nationwide to estimate the degree of SMM that warrant measures to block new transmission of malaria.

    Matched MeSH terms: Malaria, Falciparum/epidemiology
  13. Murugan K, Suresh U, Panneerselvam C, Rajaganesh R, Roni M, Aziz AT, et al.
    Environ Sci Pollut Res Int, 2018 Apr;25(11):10456-10470.
    PMID: 28913784 DOI: 10.1007/s11356-017-0074-3
    The development of novel mosquito control tools is a key prerequisite to build effective and reliable Integrated Vector Management strategies. Here, we proposed a novel method using cigarette butts for the synthesis of Ag nanostructures toxic to young instars of the malaria vector Anopheles stephensi, chloroquine (CQ)-resistant malaria parasites Plasmodium falciparum and microbial pathogens. The non-target impact of these nanomaterials in the aquatic environment was evaluated testing them at sub-lethal doses on the predatory copepod Mesocyclops aspericornis. Cigarette butt-synthesized Ag nanostructures were characterized by UV-vis and FTIR spectroscopy, as well as by EDX, SEM and XRD analyses. Low doses of cigarette butt extracts (with and without tobacco) showed larvicidal and pupicidal toxicity on An. stephensi. The LC50 of cigarette butt-synthesized Ag nanostructures ranged from 4.505 ppm (I instar larvae) to 8.070 ppm (pupae) using smoked cigarette butts with tobacco, and from 3.571 (I instar larvae) to 6.143 ppm (pupae) using unsmoked cigarette butts without tobacco. Smoke toxicity experiments conducted against adults showed that unsmoked cigarette butts-based coils led to mortality comparable to permethrin-based positive control (84.2 and 91.2%, respectively). A single treatment with cigarette butts extracts and Ag nanostructures significantly reduced egg hatchability of An. stephensi. Furthermore, the antiplasmodial activity of cigarette butt extracts (with and without tobacco) and synthesized Ag nanostructures was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of P. falciparum. The lowest IC50 values were achieved by cigarette butt extracts without tobacco, they were 54.63 μg/ml (CQ-s) and 63.26 μg/ml (CQ-r); while Ag nanostructure IC50 values were 72.13 μg/ml (CQ-s) and 77.33 μg/ml (CQ-r). In MIC assays, low doses of the Ag nanostructures inhibited the growth of Bacillus subtilis, Klebsiella pneumoniae and Salmonella typhi. Finally, the predation efficiency of copepod M. aspericornis towards larvae of An. stephensi did not decrease in a nanoparticle-contaminated environment, if compared to control predation assays. Overall, the present research would suggest that an abundant hazardous waste, such as cigarette butts, can be turned to an important resource for nanosynthesis of highly effective antiplasmodials and insecticides.
    Matched MeSH terms: Malaria, Falciparum
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