Displaying publications 81 - 100 of 308 in total

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  1. Ravindar L, Hasbullah SA, Rakesh KP, Hassan NI
    Eur J Pharm Sci, 2023 Apr 01;183:106365.
    PMID: 36563914 DOI: 10.1016/j.ejps.2022.106365
    Malaria poses a severe public health risk and a significant economic burden in disease-endemic countries. One of the most severe issues in malaria control is the development of drug resistance in malaria parasites. The standard treatment for malaria is artemisinin-combination therapy (ACT). Nevertheless, the Plasmodium parasite's extensive resistance to prior drugs and reduced ACT efficiency necessitates novel drug discovery. The progress in discovering novel, affordable, and effective antimalarial agents is significant in combating drug resistance, and the hybrid drug concept can be used to covalently link two or more active pharmacophores that may act on multiple targets. Pyrazole and pyrazoline derivatives are considered pharmacologically necessary active heterocyclic scaffolds that possess almost all types of pharmacological activities. This review summarized recent progress in antimalarial activities of synthesized pyrazole and pyrazoline derivatives. The studies published since 2000 are included in this systematic review. This review is anticipated to be beneficial for future study and new ideas in searching for rational development strategies for more effective pyrazole and pyrazoline derivatives as antimalarial drugs.
    Matched MeSH terms: Plasmodium falciparum
  2. Clyde DF, DuPont HL, Miller RM, McCarthy VC
    Trans R Soc Trop Med Hyg, 1970;64(6):834-8.
    PMID: 4924648
    Matched MeSH terms: Plasmodium falciparum*
  3. Fong T
    Mod Med Asia, 1977 Sep;13(9):14-6.
    PMID: 340882
    Matched MeSH terms: Plasmodium falciparum
  4. 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: Plasmodium falciparum/genetics*; Plasmodium falciparum/physiology*
  5. Lee WC, Russell B, Sobota RM, Ghaffar K, Howland SW, Wong ZX, et al.
    Elife, 2020 Feb 18;9.
    PMID: 32066522 DOI: 10.7554/eLife.51546
    In malaria, rosetting is described as a phenomenon where an infected erythrocyte (IRBC) is attached to uninfected erythrocytes (URBC). In some studies, rosetting has been associated with malaria pathogenesis. Here, we have identified a new type of rosetting. Using a step-by-step approach, we identified IGFBP7, a protein secreted by monocytes in response to parasite stimulation, as a rosette-stimulator for Plasmodium falciparum- and P. vivax-IRBC. IGFBP7-mediated rosette-stimulation was rapid yet reversible. Unlike type I rosetting that involves direct interaction of rosetting ligands on IRBC and receptors on URBC, the IGFBP7-mediated, type II rosetting requires two additional serum factors, namely von Willebrand factor and thrombospondin-1. These two factors interact with IGFBP7 to mediate rosette formation by the IRBC. Importantly, the IGFBP7-induced type II rosetting hampers phagocytosis of IRBC by host phagocytes.
    Matched MeSH terms: Plasmodium falciparum/physiology*
  6. Naik DG
    Trop Parasitol, 2020 05 20;10(1):3-6.
    PMID: 32775284 DOI: 10.4103/tp.TP_17_18
    Malaria, a mosquito-transmitted parasitic disease, has been targeted for elimination in many parts of the world. For many years, Plasmodium vivax, Plasmodium falciparum, Plasmodium ovale and Plasmodium malariae have been known to cause malaria in humans. Now, Plasmodium knowlesi is considered to be an important cause of malaria, especially in Southeast Asia. The emergence of P. knowlesi with zoonotic implication is a challenge in the elimination efforts of malaria in Southeast Asia. P. knowlesi is known to cause severe complicated malaria in humans. P. knowlesi parasite is transmitted between humans and wild macaque through mosquito vectors. It appears that the malaria disease severity and host immune evasion depend on antigenic variation exhibited at the surface of the infected erythrocyte. P. knowlesi is sensitive to antimalarial drug artemisinin. Identification of vector species, their biting behavior, timely correct diagnosis, and treatment are important steps in disease management and control. There is a need to identify and implement effective intervention measures to cut the chain of transmissions from animals to humans. The zoonotic malaria definitely poses a significant challenge in elimination and subsequent eradication of all types of malaria from this globe.
    Matched MeSH terms: Plasmodium falciparum
  7. van Schalkwyk DA, Blasco B, Davina Nuñez R, Liew JWK, Amir A, Lau YL, et al.
    PMID: 30831468 DOI: 10.1016/j.ijpddr.2019.02.004
    New antimalarial agents are identified and developed after extensive testing on Plasmodium falciparum parasites that can be grown in vitro. These susceptibility studies are important to inform lead optimisation and support further drug development. Until recently, little was known about the susceptibility of non-falciparum species as these had not been adapted to in vitro culture. The recent culture adaptation of P. knowlesi has therefore offered an opportunity to routinely define the drug susceptibility of this species, which is phylogenetically closer to all other human malarias than is P. falciparum. We compared the in vitro susceptibility of P. knowlesi and P. falciparum to a range of established and novel antimalarial agents under identical assay conditions. We demonstrated that P. knowlesi is significantly less susceptible than P. falciparum to six of the compounds tested; and notably these include three ATP4 inhibitors currently under development as novel antimalarial agents, and one investigational antimalarial, AN13762, which is 67 fold less effective against P. knowlesi. For the other compounds there was a less than two-fold difference in susceptibility between species. We then compared the susceptibility of a recent P. knowlesi isolate, UM01, to that of the well-established, older A1-H.1 clone. This recent isolate showed similar in vitro drug susceptibility to the A1-H.1 clone, supporting the ongoing use of the better characterised clone to further study drug susceptibility. Lastly, we used isobologram analysis to explore the interaction of a selection of drug combinations and showed similar drug interactions across species. The species differences in drug susceptibility reported by us here and previously, support adding in vitro drug screens against P. knowlesi to those using P. falciparum strains to inform new drug discovery and lead optimisation.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  8. Tan JH, Cheong FW, Lau YL, Fong MY
    Trop Biomed, 2023 Mar 01;40(1):37-44.
    PMID: 37356002 DOI: 10.47665/tb.40.1.004
    Circumsporozoite protein (CSP) central repeat region is one of the main target regions of the RTS,S/AS01 vaccine for falciparum infection as it consists of immunodominant B cell epitopes. However, there is a lack of study for P. knowlesi CSP central repeat region. This study aims to characterise the CSP repeat motifs of P. knowlesi isolates in Peninsular Malaysia. CSP repeat motifs of 64 P. knowlesi isolates were identified using Rapid Automatic Detection and Alignment of Repeats (RADAR). Antigenicity of the repeat motifs and linear B cell epitopes were predicted using VaxiJen 2.0, BepiPred-2.0 and BCPred, respectively. A total of 35 dominant repeat motifs were identified. The repeat motif "AGQPQAQGDGANAGQPQAQGDGAN" has the highest repeat frequency (n=15) and antigenicity index of 1.7986. All the repeat regions were predicted as B cell epitopes. In silico approaches revealed that all repeat motifs were antigenic and consisted of B cell epitopes which could be designed as knowlesi malaria vaccine.
    Matched MeSH terms: Plasmodium falciparum
  9. Chang SP, Kramer KJ, Yamaga KM, Kato A, Case SE, Siddiqui WA
    Exp Parasitol, 1988 Oct;67(1):1-11.
    PMID: 3049134
    The gene encoding the 195,000-Da major merozoite surface antigen (gp195) of the FUP (Uganda-Palo Alto) isolate of Plasmodium falciparum, a strain widely used for monkey vaccination experiments, has been cloned and sequenced. The translated amino acid sequence of the FUP gp195 protein is closely related to the sequences of corresponding proteins of the CAMP (Malaysia) and MAD-20 (Papua New Guinea) isolates and more distantly related to those of the Wellcome (West Africa) and K1 (Thailand) isolates, supporting the proposed allelic dimorphism of gp195 within the parasite population. The prevalence of dimorphic sequences within the gp195 protein suggests that many gp195 epitopes would be group-specific. Despite the extensive differences in amino acid sequence between gp195 proteins of these two groups, the hydropathy profiles of proteins representative of both groups are very similar. The conservation of overall secondary structure shown by the hydropathy profile comparison indicates that gp195 proteins of the various P. falciparum isolates are functionally equivalent. This information on the primary structure of the FUP gp195 protein will enable us to evaluate the possible roles of conserved, group-specific and variable epitopes in immunity to the blood stage of the malaria parasite.
    Matched MeSH terms: Plasmodium falciparum/genetics*; Plasmodium falciparum/immunology; Plasmodium falciparum/isolation & purification
  10. Mahmud F, Lee PC, Abdul Wahab H, Mustaffa KMF, Leow CH, Azhar R, et al.
    Trop Biomed, 2020 Sep 01;37(3):822-841.
    PMID: 33612795 DOI: 10.47665/tb.37.3.822
    Malaria is one of the most dangerous infectious diseases due to its high infection and mortality rates, especially in the tropical belt. Plasmodium falciparum (P. falciparum), the most virulent malaria parasite in humans, was recently reported to develop resistance against the final efficient antimalarial drug, artemisinin. Little is known about the resistance mechanisms, which further complicates the problem as a proper counteraction is unable to be taken. Hence, the understanding of drug mode of action and its molecular target is valuable knowledge that needs to be considered to develop the next generation of antimalarial drugs. P. falciparum protein kinase (Pf PK) is an attractive target for antimalarial chemotherapy due to its vital roles in all P. falciparum life stages. Moreover, overall structural differences and the presence of unique Pf PKs that are absent in human kinome, suggesting specific inhibition of Pf PK without affecting human cells is achievable. To date, at least 86 eukaryotic protein kinases have been identified in P. falciparum kinome, by which less than 40 were validated as potential targets at the erythrocytes stage. In this review, recent progress of the furthest validated Pf PKs; Pf Nek-1, Pf CDPK1, Pf CDPK4, Pf PKG, and Pf CLK-3 will be briefly discussed.
    Matched MeSH terms: Plasmodium falciparum
  11. Boush MA, Djibrine MA, Mussa A, Talib M, Maki A, Mohammed A, et al.
    Sci Rep, 2020 07 30;10(1):12822.
    PMID: 32733079 DOI: 10.1038/s41598-020-69756-8
    In remote areas of malaria-endemic countries, rapid diagnostic tests (RDTs) have dramatically improved parasitological confirmation of suspected malaria cases, especially when skilled microscopists are not available. This study was designed to determine the frequency of Plasmodium falciparum isolates with histidine-rich protein 2 (pfhrp2) gene deletion as one of the possible factors contributing to the failure of PfHRP2-based RDTs in detecting malaria. A total of 300 blood samples were collected from several health centres in Nyala City, Western Sudan. The performance of PfHRP2-based RDTs in relation to microscopy was examined and the PCR-confirmed samples were investigated for the presence of pfhrp2 gene. A total of 113 out of 300 patients were P. falciparum positive by microscopy. Among them, 93.81% (106 out of 113) were positives by the PfHRP2 RDTs. Seven isolates were identified as false negative on the basis of the RDTs results. Only one isolate (0.9%; 1/113) potentially has pfhrp2 gene deletion. The sensitivity and specificity of PfHRP2-based RDTs were 93.81% and 100%, respectively. The results provide insights into the pfhrp2 gene deletion amongst P. falciparum population from Sudan. However, further studies with a large and systematic collection from different geographical settings across the country are needed.
    Matched MeSH terms: Plasmodium falciparum/genetics*; Plasmodium falciparum/isolation & purification
  12. Atroosh WM, Lau YL, Snounou G, Azzani M, Al-Mekhlafi HM
    Malar J, 2022 Jan 04;21(1):2.
    PMID: 34983529 DOI: 10.1186/s12936-021-04014-4
    BACKGROUND: Genotyping of the three Plasmodium falciparum polymorphic genes, msp1, msp2 and glurp, has been adopted as a standard strategy to distinguish recrudescence from new infection in drug efficacy clinical trials. However, the suitability of a particular gene is compromised in areas where its allelic variants distribution is significantly skewed, a phenomenon that might occur in isolated parasite populations or in areas of very low transmission. Moreover, observation of amplification bias has diminished the value of glurp as a marker.

    METHODS: The suitability of the polymorphic P. falciparum histidine-rich protein 2 (pfhrp2) gene was assessed to serve as an alternative marker using a PCR-sequencing or a PCR-RFLP protocol for genotyping of samples in drug efficacy clinical trials. The value of pfhrp2 was validated by side-by-side analyses of 5 admission-recrudescence sample pairs from Yemeni malaria patients.

    RESULTS: The outcome of the single pfhrp2 gene discrimination analysis has been found consistent with msp1, msp2 and glurp pool genotyping analysis for the differentiation of recrudescence from new infection.

    CONCLUSION: The findings suggest that under the appropriate circumstances, pfhrp2 can serve as an additional molecular marker for monitoring anti-malarials efficacy. However, its use is restricted to endemic areas where only a minority of P. falciparum parasites lack the pfhrp2 gene.

    Matched MeSH terms: Plasmodium falciparum/genetics*
  13. Callaghan PS, Siriwardana A, Hassett MR, Roepe PD
    Malar J, 2016;15(1):186.
    PMID: 27036417 DOI: 10.1186/s12936-016-1238-1
    Recent work has perfected yeast-based methods for measuring drug transport by the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT).
    Matched MeSH terms: Plasmodium falciparum
  14. Nurul AA, Rapeah S, Norazmi MN
    Trop Biomed, 2010 Apr;27(1):60-7.
    PMID: 20562815
    Proteins on the surface of Plasmodium falciparum merozoites are good targets for vaccine development against malaria because they are accessible to antibodies in the plasma. The 19 kDa C-terminus of merozoite surface protein-1 (MSP-1(19)) has been shown to induce both inhibitory as well as blocking antibodies, the latter blocking the protective effects of the former. Inhibitory antibodies bind to MSP-1(19) and inhibit merozoite invasion of red blood cells (RBC) but the binding of blocking antibodies can prevent binding of inhibitory antibodies thereby allowing the parasite to invade RBC. We constructed a synthetic version of the MSP-1(19) of the P. falciparum using mycobacterium codon usage by assembly PCR. The synthetic MSP-1(19) was mutated at various sites to promote the production of inhibitory but not blocking antibodies as previously reported. The native and mutated MSP-1(19) were cloned and expressed in Mycobacterium bovis bacille Calmette-Guerin (BCG) and the expressions of the recombinant proteins were detected by specific monoclonal antibodies (mAbs) namely, 12.10 and 1E1 against MSP-1(19) using Western blotting. The mutated MSP-1(19) protein reacted with the inhibitory mAb, 12.10, but not the blocking mAb, 1E1, paving the way for the construction of a potential recombinant BCG (rBCG) blood stage vaccine against malaria.
    Matched MeSH terms: Plasmodium falciparum/immunology; Plasmodium falciparum/metabolism*
  15. Loughland JR, Minigo G, Sarovich DS, Field M, Tipping PE, Montes de Oca M, et al.
    Sci Rep, 2017 06 01;7(1):2596.
    PMID: 28572564 DOI: 10.1038/s41598-017-02096-2
    Plasmacytoid dendritic cells (pDC) are activators of innate and adaptive immune responses that express HLA-DR, toll-like receptor (TLR) 7, TLR9 and produce type I interferons. The role of human pDC in malaria remains poorly characterised. pDC activation and cytokine production were assessed in 59 malaria-naive volunteers during experimental infection with 150 or 1,800 P. falciparum-parasitized red blood cells. Using RNA sequencing, longitudinal changes in pDC gene expression were examined in five adults before and at peak-infection. pDC responsiveness to TLR7 and TLR9 stimulation was assessed in-vitro. Circulating pDC remained transcriptionally stable with gene expression altered for 8 genes (FDR falciparum exposure despite sub-microscopic parasitaemia downregulating HLA-DR. The lack of evident pDC activation in both early infection and malaria suggests little response of circulating pDC to infection.
    Matched MeSH terms: Plasmodium falciparum/immunology*
  16. 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: Plasmodium falciparum/enzymology*
  17. Rapeah S, Dhaniah M, Nurul AA, Norazmi MN
    Trop Biomed, 2010 Dec;27(3):461-9.
    PMID: 21399587 MyJurnal
    Macrophages are involved in innate immunity against malaria due to their ability to phagocytose infected erythrocytes and produce inflammatory cytokines, which are important for controlling parasite growth during malaria infection. In this study, the ability of a recombinant BCG (rBCG) vaccine expressing the 19-kDa C-terminus of merozoite surface protein-1 (MSP1-C) of Plasmodium falciparum, to stimulate the phagocytic activity and secretion of pro-inflammatory cytokines by the macrophage cell line J774A.1 was measured at varying times. The results demonstrate the ability of the rBCG construct to activate the inflammatory action of macrophages, which is important as a first-line of defence in clearing malaria infections.
    Matched MeSH terms: Plasmodium falciparum/genetics; Plasmodium falciparum/immunology*
  18. Nogawa T, Okano A, Lim CL, Futamura Y, Shimizu T, Takahashi S, et al.
    J Antibiot (Tokyo), 2017 02;70(2):222-225.
    PMID: 27599762 DOI: 10.1038/ja.2016.113
    Matched MeSH terms: Plasmodium falciparum/drug effects
  19. Awang K, Mukhtar MR, Hadi AH, Litaudon M, Latip J, Abdullah NR
    Nat Prod Res, 2006 May 20;20(6):567-72.
    PMID: 16835089
    The alkaloidal extract of the leaves of Phoebe grandis (nees) merr. have provided two new minor alkaloids; phoebegrandine D (1), a proaporphine-tryptamine dimer, and phoebegrandine E (2), an indoloquinolizidine. This is the first report on the occurrence of an indoloquinolizidine in the Phoebe species. The crude extract also exhibited antiplasmodial activity (IC50<8 microg mL-1). The structures of the novel compounds were elucidated by spectroscopic methods, notably 2D NMR and HRMS.
    Matched MeSH terms: Plasmodium falciparum/growth & development
  20. Idris ZM, Chan CW, Kongere J, Hall T, Logedi J, Gitaka J, et al.
    Sci Rep, 2017 08 22;7(1):9123.
    PMID: 28831122 DOI: 10.1038/s41598-017-09585-4
    As markers of exposure anti-malaria antibody responses can help characterise heterogeneity in malaria transmission. In the present study antibody responses to Plasmodium falciparum AMA-1, MSP-119 and CSP were measured with the aim to describe transmission patterns in meso-endemic settings in Lake Victoria. Two cross-sectional surveys were conducted in Lake Victoria in January and August 2012. The study area comprised of three settings: mainland (Ungoye), large island (Mfangano) and small islands (Takawiri, Kibuogi, Ngodhe). Individuals provided a finger-blood sample to assess malaria infection by microscopy and PCR. Antibody response to P. falciparum was determined in 4,112 individuals by ELISA using eluted dried blood from filter paper. The overall seroprevalence was 64.0% for AMA-1, 39.5% for MSP-119, and 12.9% for CSP. Between settings, seroprevalences for merozoite antigens were similar between Ungoye and Mfangano, but higher when compared to the small islands. For AMA-1, the seroconversion rates (SCRs) ranged from 0.121 (Ngodhe) to 0.202 (Ungoye), and were strongly correlated to parasite prevalence. We observed heterogeneity in serological indices across study sites in Lake Victoria. These data suggest that AMA-1 and MSP-119 sero-epidemiological analysis may provide further evidence in assessing variation in malaria exposure and evaluating malaria control efforts in high endemic area.
    Matched MeSH terms: Plasmodium falciparum/immunology*
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