Displaying publications 1 - 20 of 66 in total

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  1. Fulltext Coordination of apicoplast transcription in a malaria parasite by internal and host cues
    Kobayashi Y, Komatsuya K, Imamura S, Nozaki T, Watanabe YI, Sato S, et al.
    Proc Natl Acad Sci U S A, 2023 Jul 11;120(28):e2214765120.
    PMID: 37406097 DOI: 10.1073/pnas.2214765120
    The malaria parasite Plasmodium falciparum has a nonphotosynthetic plastid called the apicoplast, which contains its own genome. Regulatory mechanisms for apicoplast gene expression remain poorly understood, despite this organelle being crucial for the parasite life cycle. Here, we identify a nuclear-encoded apicoplast RNA polymerase σ subunit (sigma factor) which, along with the α subunit, appears to mediate apicoplast transcript accumulation. This has a periodicity reminiscent of parasite circadian or developmental control. Expression of the apicoplast subunit gene, apSig, together with apicoplast transcripts, increased in the presence of the blood circadian signaling hormone melatonin. Our data suggest that the host circadian rhythm is integrated with intrinsic parasite cues to coordinate apicoplast genome transcription. This evolutionarily conserved regulatory system might be a future target for malaria treatment.
    Matched MeSH terms: Plasmodium falciparum/genetics
  2. Fulltext Lateral Flow Recombinase Polymerase Amplification Assays for the Detection of Human Plasmodium Species
    Lai MY, Abdul Hamid M, Jelip J, Mudin RN, Lau YL
    Am J Trop Med Hyg, 2023 May 03;108(5):882-886.
    PMID: 36913921 DOI: 10.4269/ajtmh.22-0657
    This study highlights the development of two lateral flow recombinase polymerase amplification assays for the diagnosis of human malaria. The lateral flow cassettes contained test lines that captured biotin-, 6-carboxyfluorescein, digoxigenin-, cyanine 5-, and dinitrophenyl-labeled amplicons. The overall process can be completed in 30 minutes. Recombinase polymerase amplification coupled with lateral flow had a detection limit of 1 copy/µL for Plasmodium knowlesi, Plasmodium vivax, and Plasmodium falciparum. No cross-reactivity was observed among nonhuman malaria parasites such as Plasmodium coatneyi, Plasmodium cynomolgi, Plasmodium brasilanium, Plasmodium inui, Plasmodium fragile, Toxoplasma gondii, Sarcocystis spp., Brugia spp., and 20 healthy donors. It is rapid, highly sensitive, robust, and easy to use. The result can be read without the need for special equipment and thus has the potential to serve as an effective alternative to polymerase chain reaction methods for the diagnosis of malaria.
    Matched MeSH terms: Plasmodium falciparum/genetics
  3. Fulltext The occurrence of dihydrofolate reductase (DHFR) point mutation (SER-108-->ASN-108) in Malaysian isolates of Plasmodium falciparum
    Lim PK, Tan SK, Khoo AS, Noor Rain A, Nagappan S, Mak JW
    Southeast Asian J Trop Med Public Health, 1998 Mar;29(1):27-30.
    PMID: 9740263
    Matched MeSH terms: Plasmodium falciparum/genetics*
  4. Fragmented population structure of plasmodium falciparum in a region of declining endemicity
    Anthony TG, Conway DJ, Cox-Singh J, Matusop A, Ratnam S, Shamsul S, et al.
    J Infect Dis, 2005 May 1;191(9):1558-64.
    PMID: 15809916
    The population genetic structure of Plasmodium falciparum differs between endemic regions, but the characteristics of a population recently fragmented by effective malaria control have been unknown.
    Matched MeSH terms: Plasmodium falciparum/genetics*
  5. Fulltext Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets
    Dooley NL, Chabikwa TG, Pava Z, Loughland JR, Hamelink J, Berry K, et al.
    Nat Commun, 2023 Nov 15;14(1):7387.
    PMID: 37968278 DOI: 10.1038/s41467-023-43181-7
    Plasmodium falciparum malaria drives immunoregulatory responses across multiple cell subsets, which protects from immunopathogenesis, but also hampers the development of effective anti-parasitic immunity. Understanding malaria induced tolerogenic responses in specific cell subsets may inform development of strategies to boost protective immunity during drug treatment and vaccination. Here, we analyse the immune landscape with single cell RNA sequencing during P. falciparum malaria. We identify cell type specific responses in sub-clustered major immune cell types. Malaria is associated with an increase in immunosuppressive monocytes, alongside NK and γδ T cells which up-regulate tolerogenic markers. IL-10-producing Tr1 CD4 T cells and IL-10-producing regulatory B cells are also induced. Type I interferon responses are identified across all cell types, suggesting Type I interferon signalling may be linked to induction of immunoregulatory networks during malaria. These findings provide insights into cell-specific and shared immunoregulatory changes during malaria and provide a data resource for further analysis.
    Matched MeSH terms: Plasmodium falciparum/genetics
  6. Fulltext Full-length sequence analysis of chloroquine resistance transporter gene in Plasmodium falciparum isolates from Sabah, Malaysia
    Tan LL, Lau TY, Timothy W, Prabakaran D
    ScientificWorldJournal, 2014;2014:935846.
    PMID: 25574497 DOI: 10.1155/2014/935846
    Chloroquine resistance (CQR) in falciparum malaria was identified to be associated with several mutations in the chloroquine resistance transporter gene (pfcrt) that encodes the transmembrane transporter in digestive vacuole membrane of the parasite. This study aimed to investigate the point mutations across the full-length pfcrt in Plasmodium falciparum isolates in Sabah, Malaysia. A total of 31 P. falciparum positive samples collected from Keningau, Kota Kinabalu, and Kudat, Sabah, were analyzed. pfcrt was PCR amplified and cloned prior to sequence analysis. This study showed that all the previously described 10 point mutations associated with CQR at codons 72, 74, 75, 76, 97, 220, 271, 326, 356, and 371 were found with different prevalence. Besides, two novel point mutations, I166V and H273N, were identified with 22.5% and 19.3%, respectively. Three haplotypes, namely, CVMNK (29%), CVIET (3.2%), and SVMNT (67.7%), were identified. High prevalence of SVMNT among P. falciparum isolates from Sabah showed that these isolates are closer to the P. falciparum isolates from Papua New Guinea rather than to the more proximal Southeast Asian CVIET haplotype. Full-length analysis of pfcrt showed that chloroquine resistant P. falciparum in Sabah is still prevalent despite the withdrawal of chloroquine usage since 1979.
    Matched MeSH terms: Plasmodium falciparum/genetics*
  7. Fulltext Mutational analysis of Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase genes in the interior division of Sabah, Malaysia
    Lau TY, Sylvi M, William T
    Malar J, 2013;12:445.
    PMID: 24321120 DOI: 10.1186/1475-2875-12-445
    The sulphadoxine/pyrimethamine (SDX/PYR) combination had been chosen to treat uncomplicated falciparum malaria in Malaysia for more than 30 years. Non-silent mutations in dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes are responsible for the resistance to pyrimethamine and sulphadoxine, respectively. This study reports the mutational analysis of pfdhfr and pfdhps in single Plasmodium falciparum infection isolates from the interior division of Sabah, Malaysian Borneo.
    Matched MeSH terms: Plasmodium falciparum/genetics*
  8. Fulltext Genetic variation of pfhrp2 in Plasmodium falciparum isolates from Yemen and the performance of HRP2-based malaria rapid diagnostic test
    Atroosh WM, Al-Mekhlafi HM, Al-Jasari A, Sady H, Al-Delaimy AK, Nasr NA, et al.
    Parasit Vectors, 2015;8:388.
    PMID: 26198252 DOI: 10.1186/s13071-015-1008-x
    The genetic variation in the Plasmodium falciparum histidine-rich protein 2 (pfhrp2) gene that may compromise the use of pfhrp2-based rapid diagnostic tests (RDTs) for the diagnosis of malaria was assessed in P. falciparum isolates from Yemen.
    Matched MeSH terms: Plasmodium falciparum/genetics
  9. Cloning and sequence characterisation of falcipain-2 from Plasmodium falciparum Gombak A strain (Malaysia)
    Sim TS, Loke P, Lee MA, Singh M, Flotow H
    Parasitol Res, 2001 Sep;87(9):683-6.
    PMID: 11570549
    In this study, the genome of the Plasmodium falciparum Gombak A strain was examined for the presence of a gene encoding falcipain-2, a cysteine protease, using homology-based polymerase chain reaction cloning. The nucleotide sequence obtained from the gene cloned (designated pFG1) is approximately 99% homologous to other falcipain-2 genes from different strains. Comparatively, it is 69% homologous to falcipain-3 genes. Direct cloning of the falcipain-2 gene and its resemblance to the reported corresponding mRNA transcript suggests the absence of introns in this gene. Sequence alignment and comparison revealed four amino acid differences at positions 15, 51, 59 and 414 in the falcipain-2 from P. falciparum Gombak A as compared to other falcipain-2 proteins from different strains.
    Matched MeSH terms: Plasmodium falciparum/genetics
  10. A genus- and species-specific nested polymerase chain reaction malaria detection assay for epidemiologic studies
    Singh B, Bobogare A, Cox-Singh J, Snounou G, Abdullah MS, Rahman HA
    Am J Trop Med Hyg, 1999 Apr;60(4):687-92.
    PMID: 10348249
    A nested polymerase chain reaction (PCR) assay that uses Plasmodium genus-specific primers for the initial PCR (nest 1) amplification and either genus- or species-specific primers for the nest 2 amplifications was tested on laboratory and field samples. With in vitro cultured Plasmodium falciparum-infected blood samples, it was capable of detecting six parasites/microl of blood using DNA prepared from 25-microl blood spots on filter paper. The assay was evaluated on fingerprick blood samples collected on filter paper from 129 individuals living in a malaria-endemic area in Malaysia. Malaria prevalence by genus-specific nested PCR was 35.6% (46 of 129) compared with 28.7% (37 of 129) by microscopy. The nested PCR detected seven more malaria samples than microscopy in the first round of microscopic examination, malaria in three microscopically negative samples, six double infections identified as single infections by microscopy and one triple infection identified as a double infection by microscopy. The nested PCR assay described is a sensitive technique for collecting accurate malaria epidemiologic data. When coupled with simple blood spot sampling, it is particularly useful for screening communities in remote regions of the world.
    Matched MeSH terms: Plasmodium falciparum/genetics*
  11. Clonal diversity in single isolates of Malaysian Plasmodium falciparum
    Ang HH, Chan KL, Mak JW
    Med Trop (Mars), 1996;56(4):349-51.
    PMID: 9112620
    Six clones were derived from each of five isolates of Malaysian Plasmodium falciparum and characterized with regard to susceptibility to schizontocidal drugs, chloroquine, mefloquine, and quinine. The 5 isolates were found to be resistant to chloroquine and sensitive to mefloquine and quinine. Most of the clones displayed susceptibility patterns similar to those of their parent isolate, except ST9/D8 clone which became sensitive to chloroquine, C/C10 and ST148/A5 clones which became resistant to mefloquine and to quinine respectively. This diversity in susceptibility to schizontocidal drugs would likely have been overlooked by assessment of natural uncloned isolates against antimalarial drugs.
    Matched MeSH terms: Plasmodium falciparum/genetics*
  12. Electrophoretic variations of enzyme, GDH (NADP-dependent glutamate dehydrogenase)(EC. 1.4.1.4) in characterizing clones and isolates of Malaysian Plasmodium falciparum
    Ang HH, Chan KL, Mak JW
    Korean J Parasitol, 1996 Sep;34(3):211-3.
    PMID: 8843698
    Malaysian, African and Thai Plasmodium falciparum isolates were cultured in vitro by the Trager and Jensen method (1976; 1977) and were later cloned by the limiting dilution method (Rosario, 1981). Forty-eight clones were obtained and were characterized by electrophoretic variations of GDH (NADP-dependent glutamate dehydrogenase)(EC. 1.4.1.4). It was found that they were pure clones because they possessed either GDH-1 or GDH-2 unlike their parent isolates which exhibited both GDH-1 and GDH-2.
    Matched MeSH terms: Plasmodium falciparum/genetics
  13. Assessment of the association between three pfmdr1 point mutations and chloroquine resistance in vitro of Malaysian Plasmodium falciparum isolates
    Cox-Singh J, Singh B, Alias A, Abdullah MS
    Trans R Soc Trop Med Hyg, 1995 7 1;89(4):436-7.
    PMID: 7570891
    Matched MeSH terms: Plasmodium falciparum/genetics*
  14. Diagnosis of malaria using a plate hybridization method for the detection of polymerase chain reaction products
    Hakim SL, Furuta T, Rain AN, Normaznah Y, Zamri MR, Kojima S, et al.
    Trans R Soc Trop Med Hyg, 1995 5 1;89(3):271-2.
    PMID: 7660430
    Matched MeSH terms: Plasmodium falciparum/genetics
  15. Fulltext Importance of kelch 13 C580Y mutation in the studies of artemisinin resistance in Plasmodium falciparum in Greater Mekong Subregion
    Zaw MT, Lin Z, Emran NA
    J Microbiol Immunol Infect, 2020 Oct;53(5):676-681.
    PMID: 31563454 DOI: 10.1016/j.jmii.2019.07.006
    The mortality caused by Plasmodium falciparum was reduced by Artemisinin (ART) and ART combination therapy (ACT). However, Artemisinin resistance (ART-R) emerge during 2008 in Cambodia and spread to Greater Mekong Subregion (GMS). ART-R was confirmed not to spread to India, a gateway to whole Africa. The whole genome sequencing approach of P. falciparum assumed the k13 gene encoded Kelch protein was discovered to be associated with ART-R. Of the single nucleotide polymorphisms (SNPs) of k13 gene, C580Y mutant was commonly dominant in Cambodia, Myanmar, Thailand, Laos and Vietnam and assumed to be one of strong molecular markers for ART-R in P. falciparum isolates in GMS. Literatures published between 2017 and 2018 were reviewed in this work. F446I is observed to be doubtful molecular marker as ART-R marker. Transgenic experiment showed that parasite with F446I mutation displayed prolonged clearance in respond to ART while C580Y was applied as positive control mutant. Furthermore, study of C580Y allele in four countries Cambodia, Thailand, Laos resulted in single origin whereas the parasite with this allele showed multi-origin in three Provinces of Vietnam. As artemisinin was short acting drug, the role of long acting partner drug was studied by using transgenic C580Y mutant and C580 to leave recrudescent P. falciparum. Recently, there was treatment failure with ACT in some countries in GMS. In this review, the importance of C580Y mutation in the study of ART-R was discussed.
    Matched MeSH terms: Plasmodium falciparum/genetics*
  16. Fulltext A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609
    Zhang R, Suwanarusk R, Malleret B, Cooke BM, Nosten F, Lau YL, et al.
    J Infect Dis, 2016 Jan 1;213(1):100-4.
    PMID: 26136472 DOI: 10.1093/infdis/jiv358
    Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite-infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impaired Plasmodium vivax- and Plasmodium falciparum-infected RBCs.
    Matched MeSH terms: Plasmodium falciparum/genetics
  17. Fulltext Contribution of Plasmodium knowlesi to Multispecies Human Malaria Infections in North Sumatera, Indonesia
    Lubis IND, Wijaya H, Lubis M, Lubis CP, Divis PCS, Beshir KB, et al.
    J Infect Dis, 2017 Apr 01;215(7):1148-1155.
    PMID: 28201638 DOI: 10.1093/infdis/jix091
    Background: As Indonesia works toward the goal of malaria elimination, information is lacking on malaria epidemiology from some western provinces. As a basis for studies of antimalarial efficacy, we set out to survey parasite carriage in 3 communities in North Sumatera Province.

    Methods: A combination of active and passive detection of infection was carried out among communities in Batubara, Langkat, and South Nias regencies. Finger-prick blood samples from consenting individuals of all ages provided blood films for microscopic examination and blood spots on filter paper. Plasmodium species were identified using nested polymerase chain reaction (PCR) of ribosomal RNA genes and a novel assay that amplifies a conserved sequence specific for the sicavar gene family of Plasmodium knowlesi.

    Results: Of 3731 participants, 614 (16.5%) were positive for malaria parasites by microscopy. PCR detected parasite DNA in samples from 1169 individuals (31.3%). In total, 377 participants (11.8%) harbored P. knowlesi. Also present were Plasmodium vivax (14.3%), Plasmodium falciparum (10.5%) and Plasmodium malariae (3.4%).

    Conclusions: Amplification of sicavar is a specific and sensitive test for the presence of P. knowlesi DNA in humans. Subpatent and asymptomatic multispecies parasitemia is relatively common in North Sumatera, so PCR-based surveillance is required to support control and elimination activities.

    Matched MeSH terms: Plasmodium falciparum/genetics*
  18. The return of chloroquine-sensitive Plasmodium falciparum parasites in Jazan region, southwestern Saudi Arabia over a decade after the adoption of artemisinin-based combination therapy: analysis of genetic mutations in the pfcrt gene
    Madkhali AM, Abdulhaq AA, Atroosh WM, Ghzwani AH, Zain KA, Ghailan KY, et al.
    Parasitol Res, 2021 Nov;120(11):3771-3781.
    PMID: 34561749 DOI: 10.1007/s00436-021-07323-4
    This study investigated the polymorphism in the P. falciparum chloroquine resistance transporter (pfcrt) gene 11 years after chloroquine (CQ) cessation in Jazan region, southwestern Saudi Arabia. Two hundred and thirty-five P. falciparum isolates were amplified to detect mutations in the pfcrt gene. The pfcrt 76 T molecular marker for CQ resistance was detected in 66.4% (156/235) of the isolates, while the K76 CQ-sensitive wild type was detected in 33.6%. The pfcrt 74I and pfcrt 75E point mutations were each found to be present in 56.2% of isolates, while only four isolates (1.7%) were found to carry the pfcrt 72S mutation. Moreover, four pfcrt haplotypes were identified as follows: the CVIET triple-allele (56.2%), SVMET double-allele (1.7%) and CVMNT single-allele (8.5%) mutant haplotypes and the CVMNK wild haplotype (33.6%). The analysis also revealed significant associations between the prevalence of mutant pfcrt alleles and haplotypes and the age group, governorate and nationality of the patients as well as the parasitaemia level (p falciparum strains in Jazan region over a decade after CQ discontinuation, with about one third of the isolates analysed carrying the pfcrt K76 CQ-sensitive wild allele and the CVMNK ancestral wild haplotype. Although the reintroduction of CQ cannot be recommended at present in Saudi Arabia, these findings support the rationale for a potential future role for CQ in malaria treatment. Therefore, continuous molecular and in vitro monitoring mutations of pfcrt polymorphism in Jazan region is highly recommended.
    Matched MeSH terms: Plasmodium falciparum/genetics
  19. Fulltext Plasmodium falciparum histidine rich protein 2 (pfhrp2): an additional genetic marker suitable for anti-malarial drug efficacy trials
    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*
  20. Fulltext Genomic characterization of Plasmodium falciparum genes associated with anti-folate drug resistance and treatment outcomes in eastern India: A molecular surveillance study from 2008 to 2017
    Das S, Tripathy S, Das A, Sharma MK, Nag A, Hati AK, et al.
    Front Cell Infect Microbiol, 2022;12:865814.
    PMID: 36583107 DOI: 10.3389/fcimb.2022.865814
    INTRODUCTION: After being used vigorously for the previous two decades to treat P. falciparum, chloroquine and sulfadoxine-pyrimethamine were replaced in 2009 with an artemisinin-based combination therapy (artesunate-sulfadoxine-pyrimethamine) in an effort to combat multidrug-resistant parasites.

    METHODS: We set out to assess the genetic variants of sulfadoxine-pyrimethamine resistance and the effectiveness of its treatment in eastern India prior to, during, and 6 to 8 years following the introduction of the new pharmacological regime. In 2008-2009, 318 P. falciparum-positive patients got the recommended doses of sulfadoxine-pyrimethamine. We used 379 additional isolates from 2015 to 2017 in addition to the 106 isolates from 2010. All 803 isolates from two study sites underwent in vitro sulfadoxine-pyrimethamine sensitivity testing and genomic characterisation of sulfadoxine-pyrimethamine resistance (pfdhfr and pfdhps).

    RESULTS: In Kolkata and Purulia, we observed early treatment failure in 30.7 and 14.4% of patients, respectively, whereas recrudescence was found in 8.1 and 13.4% of patients, respectively, in 2008-2009. In 2017, the proportion of in vitro pyrimethamine and sulfadoxine resistance steadily grew in Kolkata and Purulia despite a single use of sulfadoxine-pyrimethamine. Treatment failures with sulfadoxine-pyrimethamine were linked to quintuple or quadruple pfdhfr- pfdhps mutations (AICII-AGKAT, AICII-AGKAA, AICII-SGKGT, AICII-AGKAA, AICNI-AGKAA) in 2008-2009 (p < 0.001). The subsequent spread of mutant-haplotypes with higher in vitro sulfadoxine-pyrimethamine resistance (p < 0.001), such as the sextuple (dhfr-AIRNI+dhps-AGEAA, dhfr-ANRNL+dhps-AGEAA) and septuple (dhfr-AIRNI+dhps-AGEAT), mutations were observed in 2015-2017.

    DISCUSSION: This successive spread of mutations with high in vitro sulfadoxine-pyrimethamine resistance confirmed the progressive increase in antifolate resistance even after an 8-year withdrawal of sulfadoxine-pyrimethamine.

    Matched MeSH terms: Plasmodium falciparum/genetics
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