Displaying publications 1 - 20 of 307 in total

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  1. 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*
  2. 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/drug effects*; Plasmodium falciparum/genetics
  3. 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/drug effects*; Plasmodium falciparum/genetics*
  4. Zaw MT, Emran NA, Lin Z
    J Microbiol Immunol Infect, 2018 Apr;51(2):159-165.
    PMID: 28711439 DOI: 10.1016/j.jmii.2017.06.009
    BACKGROUND: In the fight against malaria caused by Plasmodium falciparum, the successes achieved by artemisinin were endangered by resistance of the parasites to the drug. Whole genome sequencing approach on artemisinin resistant parasite line discovered k13 gene associated with drug resistance. In vitro and in vivo studies indicated mutations in the k13 gene were linked to the artemisinin resistance.

    METHODOLOGY: The literatures published after April, 2015 up to December, 2016 on k13 mutant alleles for artemisinin resistance in Plasmodium falciparum and relevant literatures were comprehensively reviewed.

    RESULTS: To date, 13 non-synonymous mutations of k13 gene have been observed to have slow parasite clearance. Worldwide mapping of k13 mutant alleles have shown mutants associated with artemisinin resistance were confined to southeast Asia and China and did not invade to African countries. Although in vitro ring stage survival assay of 0-3 h was a recently developed assay, it was useful for rapid detection of artemisinin resistance associated k13 allelic marker in the parasite. Recently, dissemination of k13 mutant alleles was recommended to be investigated by identity of haplotypes. Significant characteristics of well described alleles in the reports were mentioned in this review for the benefit of future studies.

    CONCLUSION: According to the updates in the review, it can be concluded artemisinin resistance does not disseminate to India and African countries within short period whereas regular tracking of these mutants is necessary.

    Matched MeSH terms: Plasmodium falciparum/drug effects*; Plasmodium falciparum/genetics; Plasmodium falciparum/isolation & purification*
  5. Zainudin NS, Othman N, Muhi J, Abdu Sani AA, Noordin R
    Am J Trop Med Hyg, 2015 Dec;93(6):1268-73.
    PMID: 26392156 DOI: 10.4269/ajtmh.15-0333
    This study was performed to identify circulating Plasmodium falciparum proteins in patient serum, which may be useful as diagnostic markers. Depletion of highly abundant proteins from each pooled serum sample obtained from P. falciparum-infected patients and healthy individuals was performed using the Proteoseek Antibody-Based Albumin/IgG Removal Kit (Thermo Scientific, Rockford, IL). In analysis 1, the depleted serum was analyzed directly by NanoLC-MS/MS. In analysis 2, the depleted serum was separated by two-dimensional electrophoresis followed by western blot analysis. Subsequently, the selected band was analyzed by NanoLC-MS/MS. The result of analysis 1 revealed the presence of two mature erythrocyte surface antigen (MESA) proteins and chloroquine resistance transporter protein (PfCRT). In addition, analysis 2 revealed an antigenic 75-kDa band when the membrane was probed with purified IgG from the pooled serum obtained from P. falciparum-infected patients. MS/MS analysis of this protein band revealed fragments of P. falciparum MESA proteins. Thus, in this study, two different analyses revealed the presence of Plasmodium MESA protein in pooled serum from malaria patients; thus, this protein should be further investigated to determine its usefulness as a diagnostic marker.
    Matched MeSH terms: Plasmodium falciparum/immunology*
  6. Zahari A, Ablat A, Omer N, Nafiah MA, Sivasothy Y, Mohamad J, et al.
    Sci Rep, 2016;6:21517.
    PMID: 26898753 DOI: 10.1038/srep21517
    The UV-vis spectra of isocorydine 1, norisocorydine 2 and boldine 3 were studied in 2% v/v acetonitrile, at constant ionic strength (0.1 M NaCl, 35 degree Celsius). The pK(a) values of isocorydine 1 and norisocorydine 2 were 11.75 and 12.07, respectively. Boldine 3 gave a pK(a) value of 9.16 and 10.44. All of the alkaloids 1-3 were stable at physiological pH; thereby all of them will not ionize, thus permitting the basic nitrogen to be protonated and accumulated within the acidic food vacuole of Plasmodium via pH trapping. Subsequently, acidic food vacuoles that have been neutralized by alkaloids would result in enhancement of the antiplasmodial activity. The alkaloids showed antiplasmodial activity against Plasmodium falciparum and antioxidant activities; DPPH radical scavenging, metal chelating and ferric reducing power. The antioxidant properties of the alkaloids under investigation revealed that in addition to the antiplasmodial activity, the alkaloids can also prevent oxidative damage. It can be prevented by binding free heme and neutralizing the electrons produced during the Plasmodium falciparum mediated haemoglobin destruction in the host. Slightly basic properties of the aforementioned alkaloids, along with their antioxidant activities, are advantageous in improving the suppression of malaria infection that cause less damage to the host.
    Matched MeSH terms: Plasmodium falciparum
  7. Zahari A, Cheah FK, Mohamad J, Sulaiman SN, Litaudon M, Leong KH, et al.
    Planta Med, 2014 May;80(7):599-603.
    PMID: 24723007 DOI: 10.1055/s-0034-1368349
    The crude extract of the bark of Dehaasia longipedicellata exhibited antiplasmodial activity against the growth of Plasmodium falciparum K1 isolate (resistant strain). Phytochemical studies of the extract led to the isolation of six alkaloids: two morphinandienones, (+)-sebiferine (1) and (-)-milonine (2); two aporphines, (-)-boldine (3) and (-)-norboldine (4); one benzlyisoquinoline, (-)-reticuline (5); and one bisbenzylisoquinoline, (-)-O-O-dimethylgrisabine (6). Their structures were determined on the basis of 1D and 2D NMR, IR, UV, and LCMS spectroscopic techniques and upon comparison with literature values. Antiplasmodial activity was determined for all of the isolated compounds. They showed potent to moderate activity with IC50 values ranging from 0.031 to 30.40 µM. (-)-O-O-dimethylgrisabine (6) and (-)-milonine (2) were the two most potent compounds, with IC50 values of 0.031 and 0.097 µM, respectively, that were comparable to the standard, chloroquine (0.090 µM). The compounds were also assessed for their antioxidant activities with di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (IC50 = 18.40-107.31 µg/mL), reducing power (27.40-87.40 %), and metal chelating (IC50 = 64.30 to 257.22 µg/mL) having good to low activity. (-)-O-O-dimethylgrisabine (6) exhibited a potent antioxidant activity of 44.3 % reducing power, while di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium and metal chelating activities had IC50 values of 18.38 and 64.30 µg/mL, respectively. Thus it may be considered as a good reductant with the ability to chelate metal and prevent pro-oxidant activity. In addition to the antiplasmodial and antioxidant activities, the isolated compounds were also tested for their cytotoxicity against a few cancer and normal cell lines. (-)-Norboldine (4) exhibited potent cytotoxicity towards pancreatic cancer cell line BxPC-3 with an IC50 value of 27.060 ± 1.037 µM, and all alkaloids showed no toxicity towards the normal pancreatic cell line (hTERT-HPNE).
    Matched MeSH terms: Plasmodium falciparum/drug effects*; Plasmodium falciparum/growth & development
  8. Yapp DT, Yap SY
    J Ethnopharmacol, 2003 Mar;85(1):145-50.
    PMID: 12576213
    Malaria remains a global problem in the light of chloroquine-resistant strains of Plasmodium falciparum. New compounds are needed for the development of novel antimalarial drugs. Seed, leaf, and fruit skin extracts of Lansium domesticum, a common fruit tree in South-East Asia, are used by indigenous tribes in Sabah, Malaysia for treating malaria. The skin and aqueous leaf extracts of the tree were found to reduce parasite populations of the drug sensitive strain (3D7) and the chloroquine-resistant strain (T9) of P. falciparum equally well. The skin extracts were also found to interrupt the lifecycle of the parasite. The data reported here indicate that extracts of L. domesticum are a potential source for compounds with activity towards chloroquine-resistant strains of P. falciparum.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  9. Yadav M, Prasad U
    PMID: 6095462
    The antibody titres to P. falciparum and Epstein-Barr Virus-associated antigens were assayed in 22 patients with NPC and 43 controls. All, but one patient had antimalarial titres; 14 had titres greater than 80 and 4 patients greater than 640. Compared to controls the mean anti-malarial titre for most age groups were higher in the patients. Those patients with high anti-malarial titres also had high IgA anti-VCA titre, an antibody which has been demonstrated to be diagnostic for NPC. The peak anti-VCA (IgG) and anti-EA (IgG) antibody titres were associated with anti-falciparum titres of 320-640 and 80-160, respectively. The results are discussed in relation to the possible association between malarial infection and etiology of NPC.
    Matched MeSH terms: Plasmodium falciparum/immunology*
  10. Wong SK, Lim YY, Abdullah NR, Nordin FJ
    PMID: 21232161 DOI: 10.1186/1472-6882-11-3
    Studies have shown that the barks and roots of some Apocynaceae species have anticancer and antimalarial properties. In this study, leaf extracts of five selected species of Apocynaceae used in traditional medicine (Alstonia angustiloba, Calotropis gigantea, Dyera costulata, Kopsia fruticosa and Vallaris glabra) were assessed for antiproliferative (APF) and antiplasmodial (APM) activities, and analysed for total alkaloid content (TAC), total phenolic content (TPC) and radical-scavenging activity (RSA). As V. glabra leaf extracts showed wide spectrum APF and APM activities, they were further screened for saponins, tannins, cardenolides and terpenoids.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  11. Wong JW, Yuen KH, Nagappan S, Shahul WS, Ho SS, Gan EK, et al.
    J Pharm Pharmacol, 2003 Feb;55(2):193-8.
    PMID: 12631411
    We have evaluated the therapeutic equivalence of a beta-cyclodextrin-artemisinin complex at an artemisinin dose of 150 mg, with a commercial reference preparation, Artemisinin 250 at a recommended dose of 250 mg. One hundred uncomplicated falciparum malarial patients were randomly assigned to orally receive either beta-cyclodextrin-artemisinin complex (containing 150 mg artemisinin) twice daily for five days or the active comparator (containing 250 mg artemisinin) twice daily for five days. The patients were hospitalized for seven days and were required to attend follow up assessments on days 14, 21, 28 and 35. All patients in both treatment groups were cured of the infection and achieved therapeutic success. At day seven of treatment, all patient blood was clear of the parasites and the sublingual temperature of all patients was less than 37.5 degrees C. Moreover, the parasite clearance time in both treatment groups was similar, being approximately three days after initiation of treatment. Comparable plasma artemisinin concentrations were observed between patients in both treatment groups at 1.5 and 3.0 h, although slightly higher levels were obtained with patients in the beta-cyclodextrin-artemisinin complex-treated group. The beta-cyclodextrin-artemisinin complex at a dose of 150 mg artemisinin was therapeutically equivalent to 250 mg Artemisinin 250. Additionally, patients receiving beta-cyclodextrin-artemisinin complex showed less variability in their plasma artemisinin concentrations at 1.5 h post-dosing, which suggested a more consistent rate of drug absorption.
    Matched MeSH terms: Plasmodium falciparum/drug effects
  12. Wilson T, Edeson JFB
    Br Med J, 1953;1:731.
    A letter from Drs. G. I. Robertson, D. G. Davey, and Sir Hamilton Fairley (December 6, 1952, p. 1255) reported that a proguanil-resistant strain of Plasmodium falciparum from Malaya had proved to be resistant also to pyrimethamine (" daraprim "). Proguanil-resistance in Malayan strains of P. falciparum has been recognized since 19491; and if a true cross-resistance exists, this might-as implied by Dr. J. S. K. Boyd (February 7, p. 337)-go far to explain the pyrimethamine failures described in our paper (January 31, p. 253). Proguanil has been so widely used throughout Malaya for the past six years that there can be few strains of parasite which have not yet come into contact with it; thus there is little chance of deciding now how the "parent" strains (without previous contact with proguanil) might have responded to pyrimethamine. We have not, however, been able to confirm that there is any consistent cross-resistance between these two drugs in naturally acquired falciparum malaria since pyrimethamine was first used in Malaya in 1951. Pyrimethamine failures have been successfully treated with normal doses of proguanil, and proguanilresistant infections have responded readily to pyrimethamine. In some of these cases an interval of several days was allowed to elapse between treatments, so the possibility of a combined action of the two drugs should have 'been small. We consider that these apparently conflicting results can best be explained by assuming that some present-day strains of P. falciparum in Malaya possess a " natural" resistance to pyrimethamine, whether or not any particular strain is also demonstrably resistant to proguanil. With this species of parasite, a true cross-resistance has still to be proved. REFERENCE 1 British Medical Journal, 1950. 1, 147.
    Matched MeSH terms: Plasmodium falciparum
  13. William T, Rahman HA, Jelip J, Ibrahim MY, Menon J, Grigg MJ, et al.
    PLoS Negl Trop Dis, 2013;7(1):e2026.
    PMID: 23359830 DOI: 10.1371/journal.pntd.0002026
    BACKGROUND: The simian parasite Plasmodium knowlesi is a common cause of human malaria in Malaysian Borneo and threatens the prospect of malaria elimination. However, little is known about the emergence of P. knowlesi, particularly in Sabah. We reviewed Sabah Department of Health records to investigate the trend of each malaria species over time.

    METHODS: Reporting of microscopy-diagnosed malaria cases in Sabah is mandatory. We reviewed all available Department of Health malaria notification records from 1992-2011. Notifications of P. malariae and P. knowlesi were considered as a single group due to microscopic near-identity.

    RESULTS: From 1992-2011 total malaria notifications decreased dramatically, with P. falciparum peaking at 33,153 in 1994 and decreasing 55-fold to 605 in 2011, and P. vivax peaking at 15,857 in 1995 and decreasing 25-fold to 628 in 2011. Notifications of P. malariae/P. knowlesi also demonstrated a peak in the mid-1990s (614 in 1994) before decreasing to ≈ 100/year in the late 1990s/early 2000s. However, P. malariae/P. knowlesi notifications increased >10-fold between 2004 (n = 59) and 2011 (n = 703). In 1992 P. falciparum, P. vivax and P. malariae/P. knowlesi monoinfections accounted for 70%, 24% and 1% respectively of malaria notifications, compared to 30%, 31% and 35% in 2011. The increase in P. malariae/P. knowlesi notifications occurred state-wide, appearing to have begun in the southwest and progressed north-easterly.

    CONCLUSIONS: A significant recent increase has occurred in P. knowlesi notifications following reduced transmission of the human Plasmodium species, and this trend threatens malaria elimination. Determination of transmission dynamics and risk factors for knowlesi malaria is required to guide measures to control this rising incidence.

    Matched MeSH terms: Plasmodium falciparum/isolation & purification
  14. Wernsdorfer WH, Ismail S, Chan KL, Congpuong K, Wernsdorfer G
    Wien Klin Wochenschr, 2009 Oct;121 Suppl 3:23-6.
    PMID: 19915812 DOI: 10.1007/s00508-009-1230-7
    The habitats of Eurycoma longifolia Jack, a slender tree, are jungles in Malaysia and Indonesia. It belongs to the family Simaroubaceae and is a source of quassinoids with anabolic, antimalarial and cytostatic activity. In this study, conducted during 2008 in Mae Sot, Thailand, a standardized extract of E. longifolia containing three major quassinoids, eurycomanone (1), 13,21-dihydroeurycomanone (2) and 13alpha(21)-epoxyeurycomanone (3) was evaluated for antiplasmodial activity against Plasmodium falciparum and its activity has been compared with that of artemisinin, using 38 fresh parasite isolates and assessment of inhibition of schizont maturation. The IC(50), IC(90) and IC(99) values for artemisinin were 4.30, 45.48 and 310.97 microg/l, and those for the root extract from E. longifolia 14.72, 139.65 and 874.15 microg/l respectively. The GMCOC for artemisinin was 337.81 mug/l, and for the plant extract it was 807.41 microg/l. The log-concentration probit regressions were parallel. The inhibitory activity of the E. longifolia extract was higher than that expected from the three quassinoids isolated from the plant, suggesting synergism between the quassinoids or the presence of other unidentified compounds.
    Matched MeSH terms: Plasmodium falciparum/drug effects*; Plasmodium falciparum/physiology*
  15. Wan Omar Abdullah, Ngah Zasmy Unyah, Rukman Awang Hamat, Baharudin Omar, Mohamed Kamel Abd Ghani, Mohammad Rayani, et al.
    MyJurnal
    Dichloromethane and methanolic extracts of each plant were tested for their antiplasmodial activity on chloroquineresistant strain of Plasmodium falciparum (FCB strain), based on lactate dehydrogenase activity. Cytotoxicity was assessed with the MTT test on MRC-5 human diploid embryonic lung cells. Most extracts of ten selected plants used in Malay traditional medicine in Malaysia had activity in vitro. This supports continued investigations of traditional medicine in the search for new antimalarial agent. The compounds responsible for the observed antiplasmodial effects are under investigation.
    Matched MeSH terms: Plasmodium falciparum
  16. Wahedi JA, Ande AT, Oduola AO, Obembe A, Tola M, Oyeniyi TA, et al.
    Trop Biomed, 2020 Sep 01;37(3):637-649.
    PMID: 33612778 DOI: 10.47665/tb.37.3.637
    Studies profiling community and zonal malaria entomological risk indices are required to identify high risk areas where targeted control resources are most needed or likely to have the greatest impact on reducing risk of malaria infection. This study presents a first report on malaria vector risk indices in two vegetation zones within Adamawa state, Nigeria. Endophilic mosquitoes were collected for one year in selected communities in the Guinea and Sudan savanna zones within the State. Plasmodium falciparum Sporozoite and human blood meal ELISA assays were carried out on the female Anopheles mosquitoes collected. Sibling species composition of the An. gambiae complex were determined using PCR assays. Mean numbers of mosquitoes in the Guinea savanna communities were significantly (t = 7.73, DF = 11, p < 0.001) higher than the Sudan. Man-biting rates (F = 2.76, p = 0.13) of Anopheles mosquitoes were higher in the Guinea but not significantly different from Sudan savanna. Sporozoite rates of mosquitoes within the Guinea savanna were 2.7 times higher than the Sudan. The predominant Anopheles coluzzii species encountered in the state had higher overall human blood indices (0.63) and sporozoite rates (6.9%) compared to An. gambiae (0.39, 1.9%) and An. arabiensis (0.58, 2.3%) respectively. Overall annual human blood indices (0.59) of mosquitoes in Adamawa were lower compared to reports from other States. Prevalence and higher transmission risks indices of endophilic An. coluzzii mosquitoes reveal the need for LLIN and management of relatively permanent An. coluzzii breeding sites in the State. Widespread cattle rearing lifestyle and lower human blood indices of mosquitoes in the study area suggest the need to investigate cattle blood indices of the mosquitoes in the state. Higher entomological risk indices in the Guinea Savanna zone provide baseline information for prioritization of malaria vector control supplies within the State.
    Matched MeSH terms: Plasmodium falciparum
  17. WHARTON RH, LAING AB, CHEONG WH
    Ann Trop Med Parasitol, 1963 Jun;57:235-54.
    PMID: 14042655
    Matched MeSH terms: Plasmodium falciparum*
  18. Vythilingam I, Sidavong B, Chan ST, Phonemixay T, Vanisaveth V, Sisoulad P, et al.
    Trans R Soc Trop Med Hyg, 2005 Nov;99(11):833-9.
    PMID: 16112154
    Surveys were conducted in malaria-endemic villages in the southern province of Attapeu, Lao PDR during various seasons over a 3-year period. All-night mosquito landing collections, blood surveys and a case-control study were conducted. Plasmodium falciparum was the predominant species, and slide positivity rates were higher during the transition/dry season compared with the wet season. Anopheles dirus A was found to be the primary vector, and sporozoite rates were highest during the transition/dry season. Anopheles dirus was found to be endophagic and endophilic. Not using insecticide-treated bed nets, houses close to breeding sites and sleeping away from home were risk factors associated with malaria.
    Matched MeSH terms: Plasmodium falciparum/isolation & purification; Plasmodium falciparum/parasitology*
  19. Vythilingam I, Nitiavathy K, Yi P, Bakotee B, Hugo B, Singh B, et al.
    PMID: 10928352
    Dried Anopheles farauti mosquitos caught in Solomon Islands in 1990 were examined for malaria sporozoites by ELISA and nested polymerase chain reaction (PCR). Only heads and thoraces were used. Plasmodium genus-specific nested PCR amplifications were carried out on all samples. Of the 402 pools of mosquitos that were processed, 30 were positive for malaria. Nest 1 products of positive samples were subjected to further PCR amplifications with species-specific primers for P. falciparum and P. vivax. Twenty pools were positive for P. vivax by PCR while only 7 were positive by ELISA. For P. falciparum 2 pools were positive by both ELISA and PCR, and one of these was a pool which was positive for P. vivax by PCR and ELISA. Thus the sensitivity of PCR for P. vivax was 100% while the specificity was 96.7%. For P. falciparum the sensitivity and specificity were 100%. The PCR technique is highly sensitive and can be used on dried mosquitos which makes it a valuable tool for determining sporozoite rates of mosquitos, even in remote areas.
    Matched MeSH terms: Plasmodium falciparum/growth & development; Plasmodium falciparum/isolation & purification*
  20. Tindall SM, Vallières C, Lakhani DH, Islahudin F, Ting KN, Avery SV
    Sci Rep, 2018 02 06;8(1):2464.
    PMID: 29410428 DOI: 10.1038/s41598-018-20816-0
    Antimalarial drug resistance hampers effective malaria treatment. Critical SNPs in a particular, putative amino acid transporter were recently linked to chloroquine (CQ) resistance in malaria parasites. Here, we show that this conserved protein (PF3D7_0629500 in Plasmodium falciparum; AAT1 in P. chabaudi) is a structural homologue of the yeast amino acid transporter Tat2p, which is known to mediate quinine uptake and toxicity. Heterologous expression of PF3D7_0629500 in yeast produced CQ hypersensitivity, coincident with increased CQ uptake. PF3D7_0629500-expressing cultures were also sensitized to related antimalarials; amodiaquine, mefloquine and particularly quinine. Drug sensitivity was reversed by introducing a SNP linked to CQ resistance in the parasite. Like Tat2p, PF3D7_0629500-dependent quinine hypersensitivity was suppressible with tryptophan, consistent with a common transport mechanism. A four-fold increase in quinine uptake by PF3D7_0629500 expressing cells was abolished by the resistance SNP. The parasite protein localised primarily to the yeast plasma membrane. Its expression varied between cells and this heterogeneity was used to show that high-expressing cell subpopulations were the most drug sensitive. The results reveal that the PF3D7_0629500 protein can determine the level of sensitivity to several major quinine-related antimalarials through an amino acid-inhibitable drug transport function. The potential clinical relevance is discussed.
    Matched MeSH terms: Plasmodium falciparum/drug effects; Plasmodium falciparum/genetics*; Plasmodium falciparum/metabolism
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