Displaying publications 61 - 80 of 308 in total

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  1. Idris ZM, Chan CW, Mohammed M, Kalkoa M, Taleo G, Junker K, et al.
    Parasit Vectors, 2017 Apr 26;10(1):204.
    PMID: 28441959 DOI: 10.1186/s13071-017-2139-z
    BACKGROUND: Seroepidemiology can provide evidence for temporal changes in malaria transmission and is an important tool to evaluate the effectiveness of control interventions. During the early 2000s, Vanuatu experienced an acute increase in malaria incidence due to a lapse in funding for vector control. After the distribution of subsidised insecticide-treated nets (ITNs) resumed in 2003, malaria incidence decreased in the subsequent years. This study was conducted to find the serological evidence supporting the impact of ITN on exposure to Anopheles vector bites and parasite prevalence.

    METHODS: On Ambae Island, blood samples were collected from 231 and 282 individuals in 2003 and 2007, respectively. Parasite prevalence was determined by microscopy. Antibodies to three Plasmodium falciparum (PfSE, PfMSP-119, and PfAMA-1) and three Plasmodium vivax (PvSE, PvMSP-119, and PvAMA-1) antigens, as well as the Anopheles-specific salivary antigen gSG6, were detected by ELISA. Age-specific seroprevalence was analysed using a reverse catalytic modelling approach to estimate seroconversion rates (SCRs).

    RESULTS: Parasite rate decreased significantly (P 

    Matched MeSH terms: Plasmodium falciparum/immunology
  2. Byrne I, William T, Chua TH, Patterson C, Hall T, Tan M, et al.
    Sci Rep, 2023 Aug 10;13(1):12998.
    PMID: 37563178 DOI: 10.1038/s41598-023-39670-w
    Malaysia has reported no indigenous cases of P. falciparum and P. vivax for over 3 years. When transmission reaches such low levels, it is important to understand the individuals and locations where exposure risks are high, as they may be at greater risk in the case of a resurgence of transmission. Serology is a useful tool in low transmission settings, providing insight into exposure over longer durations than PCR or RDT. We ran blood samples from a 2015 population-based survey in northern Sabah, Malaysian Borneo on a multiplex bead assay. Using supervised machine learning methods, we characterised recent and historic exposure to Plasmodium falciparum and P. vivax and found recent exposure to P. falciparum to be very low, with exposure to both species increasing with age. We performed a risk-factor assessment on environmental, behavioural, demographic and household factors, and identified forest activity and longer travel times to healthcare as common risk-factors for exposure to P. falciparum and P. vivax. In addition, we used remote-sensing derived data and geostatistical models to assess environmental and spatial associations with exposure. We created predictive maps of exposure to recent P. falciparum in the study area and showed 3 clear foci of exposure. This study provides useful insight into the environmental, spatial and demographic risk factors for P. falciparum and P. vivax at a period of low transmission in Malaysian Borneo. The findings would be valuable in the case of resurgence of human malarias in the region.
    Matched MeSH terms: Plasmodium falciparum
  3. Kano S, Onda T, Matsumoto Y, Buchachart K, Krudsood S, Looareesuwan S, et al.
    PMID: 9886125
    It was reported that a 47kDa antigenic polypeptide of Plasmodium falciparum had been strongly presented by the sera from 1) imported Japanese malaria patients with severe symptoms and 2) symptomatic and parasitemic inhabitants in endemic areas in the Sudan, Malaysia and the Philippines. In the present study, we observed the reactivity of the sera from falciparum malaria patients who had been hospitalized in the Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, and compared the antibody response against the 47kDa antigenic polypeptide according to the severity of the patients. It was observed that antibodies to this molecule were more commonly shared in sera from severer patients, although the IFAT titers against the whole P. falciparum parasite antigen were lower in the group, which suggested that this antibody against the 47kDa molecule was playing a specific role at a severe stage of the infection. Determination of the immunological features of the antigenic molecules of parasites by this type of sero-epidemiological study will provide a new assay system for evaluation of immune status of individuals in different severity and suggest a way of vaccine development.
    Matched MeSH terms: Plasmodium falciparum/immunology*
  4. Thomas V, Hock SK, Leng YP
    Trop Doct, 1981 Oct;11(4):149-54.
    PMID: 7027557
    A seroepidemiological study was carried out on Orang Asli (Aborigines) children who lead a semi-nomadic life in the deep jungles of Ulu Kelantan, Malaysia. Out of a total of about 190 children below 14 years, 143 were studied. Blood was collected from finger pricks on standard "strip type" filter papers for indirect fluorescent antibody (IFA) tests with Plasmodium falciparum antigen. A positive reaction at 1:10 dilution in infants and young children was considered positive and the reasons are given. The P. falciparum antibody prevalence rate was 84.6% compared to 81.8% spleen and 43.4% parasite rates. Both P. Falciparum and P. vivax were present in children. The age-specific patterns of antibody, spleen and parasite rates were those of a hyperendemic community. There was a positive correlation between antibody and spleen rates up to the age of 9 years. In older children, the antibody rates increased while the spleen and the parasite rates dropped.
    Matched MeSH terms: Plasmodium falciparum/immunology
  5. Thomas V, Bin HK, Leng YP
    Trans R Soc Trop Med Hyg, 1980;74(3):375-80.
    PMID: 7001690
    In 1973, 2610 sera were collected from adults living in 22 localities in four states in Peninsular Malaysia and tested by IFAT for Plasmodium falciparum antibodies. A larger number of thin films were examined. The attack phase of the Malaria Eradication Programme (MEP) in these areas was started between 1968 and 1973. The results showed that the highest prevalence rates and geometrical mean reciprocal titres (CMRT) were among adults from Kelantan where the antibody prevalence varied greatly among the adults and there was active transmission in at least three areas. The values were lowest for Kedah. The P. falciparum antibody prevalence rates were higher than the parasite rates as revealed in single thin film examinations but a number of the positive sera were reactive only at low titres. The low concentration probably indicated the residual antibody from cured cases or past infections and cross reactions to P. vivax and P. malariae infections. The strong reactions probably indicated current P. falciparum transmission as shown by positive thin films. The present study showed that the antibody profile of adults, as shown by IFAT, is of considerable value in assessing the malaria situation in a given area and that it would be useful as a malariometric tool in epidemiological studies to evaluate the progress of malaria eradication/control programmes.
    Matched MeSH terms: Plasmodium falciparum/immunology
  6. Ogunfowokan O, Ogunfowokan BA, Nwajei AI
    Afr J Prim Health Care Fam Med, 2020 Jun 17;12(1):e1-e8.
    PMID: 32634015 DOI: 10.4102/phcfm.v12i1.2212
    BACKGROUND: Malaria diagnosis using microscopy is currently the gold standard. However, malaria rapid diagnostic tests (mRDTs) were developed to simplify the diagnosis in regions without access to functional microscopy.

    AIM: The objective of this study was to compare the diagnostic accuracy of mRDT CareStatTM with microscopy.

    SETTING: This study was conducted in the paediatric primary care clinic of the Federal Medical Centre, Asaba, Nigeria.

    METHODS: A cross-sectional study for diagnostic accuracy was conducted from May 2016 to October 2016. Ninety-eight participants were involved to obtain a precision of 5%, sensitivity of mRDT CareStatTM of 95% from published work and 95% level of confidence after adjusting for 20% non-response rate or missing data. Consecutive participants were tested using both microscopy and mRDT. The results were analysed using EPI Info Version 7.

    RESULTS: A total of 98 children aged 3-59 months were enrolled. Malaria prevalence was found to be 53% (95% confidence interval [CI] = 46% - 60%), whilst sensitivity and specificity were 29% (95% CI = 20% - 38%) and 89% (95% CI = 83% - 95%), respectively. The positive and negative predictive values were 75% (95% CI = 66.4% - 83.6%) and 53% (95% CI = 46% - 60%), respectively.

    CONCLUSION: Agreement between malaria parasitaemia using microscopy and mRDT positivity increased with increase in the parasite density. The mRDT might be negative when malaria parasite density using microscopy is low.

    Matched MeSH terms: Plasmodium falciparum/immunology
  7. 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: Plasmodium falciparum/drug effects*
  8. Gitaka JN, Takeda M, Kimura M, Idris ZM, Chan CW, Kongere J, et al.
    Malar J, 2017 03 02;16(1):98.
    PMID: 28253868 DOI: 10.1186/s12936-017-1743-x
    BACKGROUND: Plasmodium falciparum SURFIN4.1is a putative ligand expressed on the merozoite and likely on the infected red blood cell, whose gene was suggested to be under directional selection in the eastern Kenyan population, but under balancing selection in the Thai population. To understand this difference, surf4.1sequences of western Kenyan P. falciparum isolates were analysed. Frameshift mutations and copy number variation (CNV) were also examined for the parasites from western Kenya and Thailand.

    RESULTS: Positively significant departures from neutral expectations were detected on the surf4.1region encoding C-terminus of the variable region 2 (Var2) by 3 population-based tests in the western Kenyan population as similar in the Thai population, which was not covered by the previous analysis for eastern Kenyan population. Significant excess of non-synonymous substitutions per nonsynonymous site over synonymous substitutions per synonymous site was also detected in the Var2 region. Negatively significant departures from neutral expectations was detected on the region encoding Var1 C-terminus consistent to the previous observation in the eastern Kenyan population. Parasites possessing a frameshift mutation resulting a product without intracellular Trp-rich (WR) domains were 22/23 in western Kenya and 22/36 in Thailand. More than one copy of surf4.1gene was detected in western Kenya (4/24), but no CNV was found in Thailand (0/36).

    CONCLUSIONS: The authors infer that the high polymorphism of SURFIN4.1Var2 C-terminus in both Kenyan and Thai populations were shaped-up by diversifying selection and maintained by balancing selection. These phenomena were most likely driven by immunological pressure. Whereas the SURFIN4.1Var1 C-terminus is suggested to be under directional selection consistent to the previous report for the eastern Kenyan population. Most western Kenyan isolates possess a frameshift mutation that would limit the expression of SURFIN4.1on the merozoite, but only 60% of Thai isolates possess this frameshift, which would affect the level and type of the selection pressure against this protein as seen in the two extremities of Tajima's D values for Var1 C-terminus between Kenyan and Thai populations. CNV observed in Kenyan isolates may be a consequence of this frameshift mutation to increase benefits on the merozoite surface.

    Matched MeSH terms: Plasmodium falciparum/genetics*; Plasmodium falciparum/isolation & purification
  9. Murugan K, Samidoss CM, Panneerselvam C, Higuchi A, Roni M, Suresh U, et al.
    Parasitol Res, 2015 Nov;114(11):4087-97.
    PMID: 26227141 DOI: 10.1007/s00436-015-4638-1
    Malaria, the most widespread mosquito-borne disease, affects 350-500 million people each year. Eco-friendly control tools against malaria vectors are urgently needed. This research proposed a novel method of plant-mediated synthesis of silver nanoparticles (AgNP) using a cheap seaweed extract of Ulva lactuca, acting as a reducing and capping agent. AgNP were characterized by UV-vis spectrophotometry, Fourier transform infrared (FTIR) spectroscopy, energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The U. lactuca extract and the green-synthesized AgNP were tested against larvae and pupae of the malaria vector Anopheles stephensi. In mosquitocidal assays, LC50 values of U. lactuca extract against A. stephensi larvae and pupae were 18.365 ppm (I instar), 23.948 ppm (II), 29.701 ppm (III), 37.517 ppm (IV), and 43.012 ppm (pupae). LC50 values of AgNP against A. stephensi were 2.111 ppm (I), 3.090 ppm (II), 4.629 ppm (III), 5.261 ppm (IV), and 6.860 ppm (pupae). Smoke toxicity experiments conducted against mosquito adults showed that U. lactuca coils evoked mortality rates comparable to the permethrin-based positive control (66, 51, and 41%, respectively). Furthermore, the antiplasmodial activity of U. lactuca extract and U. lactuca-synthesized AgNP was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of Plasmodium falciparum. Fifty percent inhibitory concentration (IC50) values of U. lactuca were 57.26 μg/ml (CQ-s) and 66.36 μg/ml (CQ-r); U. lactuca-synthesized AgNP IC50 values were 76.33 μg/ml (CQ-s) and 79.13 μg/ml (CQ-r). Overall, our results highlighted out that U. lactuca-synthesized AgNP may be employed to develop newer and safer agents for malaria control.
    Matched MeSH terms: Plasmodium falciparum/physiology
  10. WHARTON RH, LAING AB, CHEONG WH
    Ann Trop Med Parasitol, 1963 Jun;57:235-54.
    PMID: 14042655
    Matched MeSH terms: Plasmodium falciparum*
  11. Min TH, Khairul MF, Low JH, Che Nasriyyah CH, A'shikin AN, Norazmi MN, et al.
    Exp Parasitol, 2007 Apr;115(4):387-92.
    PMID: 17118354
    Chloroquine (CQ) and mefloquine (MQ) are no longer potent antimalarial drugs due to the emergence of resistant Plasmodium falciparum. Combination therapy has become the standard for many regimes in overcoming drug resistance. Roxithromycin (ROM), a known p-glycoprotein inhibitor, is reported to have antimalarial activity and it is hoped it will potentiate the effects of both CQ/MQ and reverse CQ/MQ-resistance. We assayed the effects of CQ and MQ individually and in combination with ROM on synchronized P. falciparum (Dd2 strain) cultures. The IC(50) values of CQ and MQ were 60.0+/-5.0 and 16.0+/-3.0 ng/ml; these were decreased substantially when combined with ROM. Isobolograms indicate that CQ-ROM combinations were relatively more synergistic (mean FICI 0.70) than MQ-ROM (mean FICI 0.85) with their synergistic effect at par with CQ-verapamil (VRP) (mean FICI 0.64) and MQ-VRP (mean FICI 0.60) combinations. We conclude that ROM potentiates the CQ/MQ response on multidrug-resistant P. falciparum.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  12. Khan MB, Liew JW, Leong CS, Lau YL
    Parasit Vectors, 2016 Sep 29;9(1):525.
    PMID: 27688040
    Anopheles mosquitoes transmit malaria which is one of the world's most threatening diseases. Anopheles dirus (sensu stricto) is among the main vectors of malaria in South East Asia. The mosquito innate immune response is the first line of defence against malaria parasites during its development. The immune deficiency (IMD) pathway, a conserved immune signaling pathway, influences anti-Plasmodium falciparum activity in Anopheles gambiae, An. stephensi and An. albimanus. The aim of the study was to determine the role of Rel2, an IMD pathway-controlled NF-kappaβ transcription factor, in An. dirus.
    Matched MeSH terms: Plasmodium falciparum
  13. 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: Plasmodium falciparum/isolation & purification
  14. Ravichandran M, Doolan DL, Cox-Singh J, Hoffman SL, Singh B
    Parasite Immunol., 2000 Sep;22(9):469-73.
    PMID: 10972854
    Considerable effort is directed at the development of a malaria vaccine that elicits antigen-specific T-cell responses against pre-erythrocytic antigens of Plasmodium falciparum. Genetic restriction of host T-cell responses and polymorphism of target epitopes on parasite antigens pose obstacles to the development of such a vaccine. Liver stage-specific antigen-1 (LSA-1) is a prime candidate vaccine antigen and five T-cell epitopes that are degenerately restricted by HLA molecules common in most populations have been identified on LSA-1. To define the extent of polymorphism within these T-cell epitopes, the N-terminal non-repetitive region of the LSA-1 gene from Malaysian P. falciparum field isolates was sequenced and compared with data of isolates from Brazil, Kenya and Papua New Guinea. Three of the T-cell epitopes were completely conserved while the remaining two were highly conserved in the isolates examined. Our findings underscore the potential of including these HLA-degenerate T-cell epitopes of LSA-1 in a subunit vaccine.
    Matched MeSH terms: Plasmodium falciparum/immunology*; Plasmodium falciparum/isolation & purification
  15. Siti Nurfatimah Mohd Shahpudin, Doblin Anak Sandai, Sharlina Mohamad
    MyJurnal
    Protein kinases (PKs) are regulators of protein phosphorylation in many infectious diseases, including malaria. How- ever, the cellular functions of majority of PKs in Plasmodium falciparum remain unknown. The mechanisms involved in P. falciparum cell cycle progress are not fully understood. The activation of cyclin-dependent kinases (CDKs), which constitute a PK family that includes crucial regulators of cell cycle progression in eukaryotes, is strictly being coordinated by the interaction with specific cyclins at well-defined points within the cell cycle. These cyclin/CDK complexes are very well characterised in humans, but little is known in P. falciparum. This review expand our un- derstanding of the characteristic of CDKs and cyclins in P. falciparum, and paves the way for further investigations on the precise molecular role of these crucial regulatory proteins in mosquito and human. This represents a valuable step towards the elucidation of cell cycle control mechanisms in malaria parasites.
    Matched MeSH terms: Plasmodium falciparum
  16. Loughland JR, Woodberry T, Oyong D, Piera KA, Amante FH, Barber BE, et al.
    Malar J, 2021 Feb 16;20(1):97.
    PMID: 33593383 DOI: 10.1186/s12936-021-03642-0
    BACKGROUND: Plasmodium falciparum malaria increases plasma levels of the cytokine Fms-like tyrosine kinase 3 ligand (Flt3L), a haematopoietic factor associated with dendritic cell (DC) expansion. It is unknown if the zoonotic parasite Plasmodium knowlesi impacts Flt3L or DC in human malaria. This study investigated circulating DC and Flt3L associations in adult malaria and in submicroscopic experimental infection.

    METHODS: Plasma Flt3L concentration and blood CD141+ DC, CD1c+ DC and plasmacytoid DC (pDC) numbers were assessed in (i) volunteers experimentally infected with P. falciparum and in Malaysian patients with uncomplicated (ii) P. falciparum or (iii) P. knowlesi malaria.

    RESULTS: Plasmodium knowlesi caused a decline in all circulating DC subsets in adults with malaria. Plasma Flt3L was elevated in acute P. falciparum and P. knowlesi malaria with no increase in a subclinical experimental infection. Circulating CD141+ DCs, CD1c+ DCs and pDCs declined in all adults tested, for the first time extending the finding of DC subset decline in acute malaria to the zoonotic parasite P. knowlesi.

    CONCLUSIONS: In adults, submicroscopic Plasmodium infection causes no change in plasma Flt3L but does reduce circulating DCs. Plasma Flt3L concentrations increase in acute malaria, yet this increase is insufficient to restore or expand circulating CD141+ DCs, CD1c+ DCs or pDCs. These data imply that haematopoietic factors, yet to be identified and not Flt3L, involved in the sensing/maintenance of circulating DC are impacted by malaria and a submicroscopic infection. The zoonotic P. knowlesi is similar to other Plasmodium spp in compromising DC in adult malaria.

    Matched MeSH terms: Plasmodium falciparum/physiology
  17. Ravindar L, Hasbullah SA, Rakesh KP, Hassan NI
    Eur J Med Chem, 2023 Aug 05;256:115458.
    PMID: 37163950 DOI: 10.1016/j.ejmech.2023.115458
    Malaria is the fifth most lethal parasitic infection in the world. Antimalarial medications have played a crucial role in preventing and eradicating malaria. Numerous heterocyclic moieties have been incorporated into the creation of effective antimalarial drugs. The 4-aminoquinoline moiety is favoured in antimalarial drug discovery due to the diverse biological applications of its derivative. Since the 1960s, 4-aminoquinoline has been an important antimalarial drug due to its low toxicity, high tolerability, and rapid absorption after administration. This review focused on the antimalarial efficacy of the 4-aminoquinoline moiety hybridised with various heterocyclic scaffolds developed by scientists since 2018 against diverse Plasmodium clones. It could aid in the future development of more effective antimalarial agents.
    Matched MeSH terms: Plasmodium falciparum
  18. Hoon AH, Lam CK, Wah MJ
    Antimicrob Agents Chemother, 1995 Mar;39(3):626-8.
    PMID: 7793863
    Malaysian, TGR (Thailand), and Gambian (West African) Plasmodium falciparum isolates were cultured in vitro by the candle jar method and were characterized for their susceptibilities to present antimalarial drugs by the modified in vitro microtechnique. Results showed that 93 and 47% of the Malaysian isolates were resistant at 50% inhibitory concentrations of 0.1415 to 0.7737 and 0.1025 to 0.1975 microM, respectively, while the rest were susceptible to choloroquine and cycloguanil at 0.0376 and 0.0306 to 0.0954 microM, respectively. All isolates were susceptible to mefloquine, quinine, and pyrimethamine at 0.0026 to 0.0172, 0.0062 to 0.0854, and 0.0149 to 0.0663 microM, respectively. In contrast, the Gambian isolate was susceptible to multiple drugs at 0.0024 to 0.0282 microM; TGR was resistant to chloroquine at 0.8147 microM but was susceptible to mefloquine, quinine, cycloguanil, and pyrimethamine at 0.0024, 0.0096, 0.0143, and 0.0495 microM, respectively.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  19. Ang HH, Cheang HS
    Chemotherapy, 1999 Nov-Dec;45(6):446-51.
    PMID: 10567775
    Thirty clones were obtained from five Malaysian Plasmodium falciparum isolates using the limiting dilution method. These clones were then subjected to antimalarial testing using the modified in vitro microtechnique. The results showed that ST 85/B3, GC/C10 and ST 85/A2 clones decreased their susceptibilities to 19, 41 and 28% whilst ST 12/F8, ST 85/B3 and ST 85/B3 clones showed increases of 6, 43 and 21%, respectively, against chloroquine, mefloquine and quinine after cryopreservation. Further results also indicated that GC/B4, GC/B7, GC/C10, ST 85/A5, ST 85/D3, ST 148/F8 clones did not show any change (up to 2 decimal places) against chloroquine, ST 12/D5, ST 12/E8, ST 12/F8, ST 148/A5 clones against quinine after cryopreservation. They, however, maintained their original susceptibilities after cryopreservation.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  20. T Thurai Rathnam J, Grigg MJ, Dini S, William T, Sakam SS, Cooper DJ, et al.
    Malar J, 2023 Feb 14;22(1):54.
    PMID: 36782162 DOI: 10.1186/s12936-023-04483-9
    BACKGROUND: The incidence of zoonotic Plasmodium knowlesi infections in humans is rising in Southeast Asia, leading to clinical studies to monitor the efficacy of anti-malarial treatments for knowlesi malaria. One of the key outcomes of anti-malarial drug efficacy is parasite clearance. For Plasmodium falciparum, parasite clearance is typically estimated using a two-stage method, that involves estimating parasite clearance for individual patients followed by pooling of individual estimates to derive population estimates. An alternative approach is Bayesian hierarchical modelling which simultaneously analyses all parasite-time patient profiles to determine parasite clearance. This study compared these methods for estimating parasite clearance in P. knowlesi treatment efficacy studies, with typically fewer parasite measurements per patient due to high susceptibility to anti-malarials.

    METHODS: Using parasite clearance data from 714 patients with knowlesi malaria and enrolled in three trials, the Worldwide Antimalarial Resistance Network (WWARN) Parasite Clearance Estimator (PCE) standard two-stage approach and Bayesian hierarchical modelling were compared. Both methods estimate the parasite clearance rate from a model that incorporates a lag phase, slope, and tail phase for the parasitaemia profiles.

    RESULTS: The standard two-stage approach successfully estimated the parasite clearance rate for 678 patients, with 36 (5%) patients excluded due to an insufficient number of available parasitaemia measurements. The Bayesian hierarchical estimation method was applied to the parasitaemia data of all 714 patients. Overall, the Bayesian method estimated a faster population mean parasite clearance (0.36/h, 95% credible interval [0.18, 0.65]) compared to the standard two-stage method (0.26/h, 95% confidence interval [0.11, 0.46]), with better model fits (compared visually). Artemisinin-based combination therapy (ACT) is more effective in treating P. knowlesi than chloroquine, as confirmed by both methods, with a mean estimated parasite clearance half-life of 2.5 and 3.6 h, respectively using the standard two-stage method, and 1.8 and 2.9 h using the Bayesian method.

    CONCLUSION: For clinical studies of P. knowlesi with frequent parasite measurements, the standard two-stage approach (WWARN's PCE) is recommended as this method is straightforward to implement. For studies with fewer parasite measurements per patient, the Bayesian approach should be considered. Regardless of method used, ACT is more efficacious than chloroquine, confirming the findings of the original trials.

    Matched MeSH terms: Plasmodium falciparum
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