scholarly journals Evaluation of antimalarial prescription pattern and susceptibility of Plasmodium falciparum isolates in Kaduna, Nigeria

2020 ◽  
Vol 13 (7) ◽  
pp. 3398-3410
Author(s):  
O. Ifeoluwa Akanni ◽  
J.O. Ehinmidu ◽  
R.O. Bolaji
Keyword(s):  
Plasmodium Falciparum ◽  
Combination Therapy ◽  
Antimalarial Drug ◽  
Drug Prescription ◽  
Artemisinin Combination Therapy ◽  
Therapy Resistance ◽  
Antimalarial Drugs ◽  
In Vitro Susceptibility

Nigeria carries the highest burden of malaria in terms of morbidity and mortality. This is compounded by continuous resistance of Plasmodium falciparum to antimalarial drugs. This study was designed to evaluate the profile of malaria patients’ antimalarial drug prescription and in vitro susceptibility of P. falciparum isolates to commonly prescribed antimalarial drugs in Kaduna, Nigeria. Three years’ records of patients antimalarial drug prescriptions were collated (2013 to 2015) and the in vitro antimalarial agent susceptibility was determined for 28 clinical isolates using WHO Mark III microtest. Artemisinin-based combination therapy (ACT) was the most prescribed antimalarial for the period under review (92.3-93.7%). Among the ACTs, Artemether-lumefantrine was most prescribed. Of the 28 P. falciparum isolates evaluated, 3 (10.71%) were resistant to chloroquine with a median IC50 of 4.82μM (4.60-8.14μM), while five (17.86%) were resistant to mefloquine with a median IC50 of 25μM (10.3-41μM), 7(25.00%) to artemether with a median IC50 of 2.69μM (2.09-8.77μM), 9 (32.14%) to artesunate-mefloquine combination with a median IC50 of 9.0μM (7.98-35μM) and to artesunate, 11(39.29%) were resistant with a median IC50 of 2.4μM (1.56-5.65μM). This result shows a decline in resistance of P. falciparum to chloroquine compared to period prior to artemisinin-combination therapy as well as reduced susceptibility to artesunate and artemether. Further in vitro and in vivo monitoring will be required to inform antimalarial drug policy change.Keywords: Antimalarial, Artemisinin-combination therapy, resistance, susceptibility, microtest.

scholarly journals In Vitro Activity of Pyronaridine against Multidrug-Resistant Plasmodium falciparum and Plasmodium vivax

2010 ◽  
Vol 54 (12) ◽  
pp. 5146-5150 ◽  
Author(s):  
R. N. Price ◽  
J. Marfurt ◽  
F. Chalfein ◽  
E. Kenangalem ◽  
K. A. Piera ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Combination Therapy ◽  
Plasmodium Vivax ◽  
Artemisinin Combination Therapy ◽  
Rank Correlation ◽  
Multidrug Resistant ◽  
Trophozoite Stage ◽  
Nm Range

ABSTRACT Pyronaridine, a Mannich base antimalarial, has demonstrated high in vivo and in vitro efficacy against chloroquine-resistant Plasmodium falciparum. Although this drug has the potential to become a prominent artemisinin combination therapy, little is known about its efficacy against drug-resistant Plasmodium vivax. The in vitro antimalarial susceptibility of pyronaridine was assessed in multidrug-resistant P. vivax (n = 99) and P. falciparum (n = 90) isolates from Papua, Indonesia, using a schizont maturation assay. The median 50% inhibitory concentration (IC50) of pyronaridine was 1.92 nM (range, 0.24 to 13.8 nM) against P. falciparum and 2.58 nM (range, 0.13 to 43.6 nM) against P. vivax, with in vitro susceptibility correlating significantly with chloroquine, amodiaquine, and piperaquine (rs [Spearman's rank correlation coefficient] = 0.45 to 0.62; P < 0.001). P. falciparum parasites initially at trophozoite stage had higher IC50s of pyronaridine than those exposed at the ring stage (8.9 nM [range, 0.6 to 8.9 nM] versus 1.6 nM [range, 0.6 to 8.9 nM], respectively; P = 0.015), although this did not reach significance for P. vivax (4.7 nM [range, 1.4 to 18.7 nM] versus 2.5 nM [range, 1.4 to 15.6 nM], respectively; P = 0.085). The excellent in vitro efficacy of pyronaridine against both chloroquine-resistant P. vivax and P. falciparum highlights the suitability of the drug as a novel partner for artemisinin-based combination therapy in regions where the two species are coendemic.

scholarly journals Potensi Daun Kastuba (Euphorbia Pulcherrima) Sebagai Antimalaria Plasmodium Falciparum

2020 ◽  
Vol 18 (1) ◽  
pp. 1
Author(s):  
ELVINA VERONICA ◽  
NI KADEK SINTA DWI CHRISMAYANTI
Keyword(s):  
Plasmodium Falciparum ◽  
Literature Review ◽  
Combination Therapy ◽  
In Silico ◽  
Artemisinin Combination Therapy ◽  
Ornamental Plants ◽  
Google Scholar ◽  
Euphorbia Pulcherrima

<p><strong>Abstract</strong></p><p><strong>Introduction:</strong> Around 41% of people in the world at risk of malaria due to plasmodium infection. <em>Plasmodium falciparum</em> is the most dangerous malaria infection compared to another plasmodium because it causes 90% of malaria deaths. ACT (Artemisinin Combination Therapy) is the goal standard of malaria medicine, is starting to become resistant, so other alternatives are needed. Poinsettia plants (<em>Euphorbia pulcherrima</em>) are ornamental plants and contain compounds that potential as anti-parasites.</p><p><strong>Objective:</strong> To aims the potential of poinsettia leaves as an antimalarial alternative to <em>Plasmodium falciparum</em> in malaria treatment.</p><p><strong>Methods:</strong> Literature studies using in vivo, in vitro, in silico research articles, and literature reviews from national and international journals accessed from Google Scholar, Elsevier, Science Direct, and Pubmed in the last 10 years using malaria, antioxidants, anti-malaria, <em>Plasmodium falciparum</em>, and <em>Euphorbia pulcherrima</em> as keywords. There were 22 relevant articles used in this literature review.</p><p><strong>Results:</strong> Antioxidants in poinsettia leaves inhibited plasmodium growth by inhibit nutrient transport at new permeation pathways and prevent hemozoin ban. Terpenoids in poinsettia inhibit schizont and trophozoite in an earlier asexual phase of <em>Plasmodium falciparum</em> by inhibiting isoprenoid biosynthesis.</p><p><strong>Conclusion:</strong> Poinsettia (<em>Euphorbia pulcherrima</em>) has the potency to be an antimalarial alternative against <em>Plasmodium falciparum</em>. Need further research about the dosage and side effects of the usage.</p><p><strong>Key words:</strong> Malaria, antioxidants, anti-malaria, <em>Plasmodium falciparum</em>, <em>Euphorbia pulcherrima</em></p><p><strong>Abstrak</strong></p><p><strong>Pendahuluan:</strong> Sebesar 41% penduduk di dunia berisiko terkena malaria akibat infeksi plasmodium. Infeksi malaria akibat <em>Plasmodium falciparum</em> merupakan infeksi paling berbahaya dibandingkan plasmodium lainnya karena menyebabkan 90% kematian malaria. obat malaria ACT (<em>Artemisinin Combination Therapy</em>) yang merupakan pengobatan goal standar obat malaria kini mulai resistensi sehingga diperlukan alternatif lainnya. Tanaman kastuba (<em>Euphorbia pulcherrima</em>) merupakan tanaman hias dan memiliki kandungan senyawa antioksidan yang berpotensi sebagai anti parasit.</p><p><strong>Tujuan</strong>: mengetahui potensi daun kastuba sebagai alternatif antimalarial <em>Plasmodium falciparum</em> dalam pengobatan malaria.</p><p>Metode: Studi literatur menggunakan artikel penelitian in vivo, in vitro, in silico, dan artikel tinjauan pustaka dari jurnal nasional dan internasional yang diakses dari Google Scholar, Elsevier, Science Direct, dan Pubmed 10 tahun terakhir menggunakan kata kunci malaria, antioksidan, anti-malaria, <em>Plasmodium falciparum</em>, <em>Euphorbia pulcherrima</em>. Digunakan 22 artikel yang relevan dalam <em>literature review</em> ini.</p><p><strong>Hasil:</strong> Antioksidan tanaman kastuba menghambat perkembangan plasmodium dengan menghambat transport nutrisi jalur permeasi baru dan mencegah pembentukan hemozoin. Terpenoid dalam tanaman kastuba menghambat pembentukan skizon dan tropozoit fase aseksual <em>Plasmodium falciparum</em> dengan menghambat biosintesis isoprenoid.</p><p><strong>Kesimpulan:</strong> Tanaman kastuba (<em>Euphorbia pulcherrima</em>) berpotensi sebagai alternatif antimalarial terhadap <em>Plasmodium falciparum</em>. Perlu penelitian lebih lanjut terutama dalam dosis dan efek samping penggunaannya.</p><p><strong>Kata kunci</strong>: Malaria, antioksidan,<em> anti-malaria, Plasmodium falciparum, Euphorbia pulcherrima </em></p>

scholarly journals Stable Artesunate Resistance in A Humanized Mouse Model of Plasmodium falciparum

2021 ◽  
Author(s):  
Sheetal Saini ◽  
Rajinder Kumar ◽  
Rajeev K. Tyagi
Keyword(s):  
Plasmodium Falciparum ◽  
Combination Therapy ◽  
Malaria Infection ◽  
Artemisinin Resistance ◽  
Antimalarial Drugs ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Human Malaria

Plasmodium falciparum, the most devastating human malaria parasite, confers higher morbidity and mortality. Although efforts have been made to develop an effective malaria vaccine, stage- and species-specific short-lived immunity crippled these efforts. Hence, antimalarial drug treatment becomes a mainstay for the treatment of malaria infection in the wake of the unavailability of an effective vaccine. Further, there has been a wide array of antimalarial drugs effective against various developmental stages of P. falciparum due to their different structures, modes of action, and pharmacodynamics as well as pharmacokinetics. The development of resistance against almost all frontline drugs by P. falciparum indicates the need for combination therapy (artemisinin-based combination therapy; ACT) to treat patients with P. falciparum. A higher pool of parasitemia under discontinuous in vivo artemisinin drug pressure in a developed humanized mouse allows the selection of artesunate resistant (ART-R) P. falciparum. Intravenously administered artesunate, using either single flash doses or a 2-day regimen, to the P. falciparum-infected human blood chimeric NOD/SCID.IL-2Rγ−/− immunocompromised (NSG) mice, with progressive dose increments upon parasite recovery, was the strategy deployed to select resistant parasites. Parasite susceptibility to artemisinins and other antimalarial compounds was characterized in vitro and in vivo. P. falciparum has shown to evolve extreme artemisinin resistance as well as co-resistance to antimalarial drugs. Overall, the present information shall be very useful in devising newer therapeutic strategies to treat human malaria infection.

scholarly journals Absence of Association between Methylene Blue Reduced Susceptibility and Polymorphisms in 12 Genes Involved in Antimalarial Drug Resistance in African Plasmodium falciparum

2021 ◽  
Vol 14 (4) ◽  
pp. 351
Author(s):  
Mathieu Gendrot ◽  
Océane Delandre ◽  
Marie Robert ◽  
Francis Foguim ◽  
Nicolas Benoit ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Antimalarial Drug ◽  
Antimalarial Drugs ◽  
New Drugs ◽  
Cross Resistance ◽  
Antimalarial Drug Resistance ◽  
In Vitro Susceptibility

Half the human population is exposed to malaria. Plasmodium falciparum antimalarial drug resistance monitoring and development of new drugs are major issues related to the control of malaria. Methylene blue (MB), the oldest synthetic antimalarial, is again a promising drug after the break of its use as an antimalarial drug for more than 80 years and a potential partner for triple combination. Very few data are available on the involvement of polymorphisms on genes known to be associated with standard antimalarial drugs and parasite in vitro susceptibility to MB (cross-resistance). In this context, MB susceptibility was evaluated against 482 isolates of imported malaria from Africa by HRP2-based ELISA chemosusceptibility assay. A total of 12 genes involved in antimalarial drug resistance (Pfcrt, Pfdhfr, Pfmdr1, Pfmdr5, Pfmdr6, PfK13, Pfubq, Pfcarl, Pfugt, Pfact, Pfcoronin, and copy number of Pfpm2) were sequenced by Sanger method and quantitative PCR. On the Pfmdr1 gene, the mutation 86Y combined with 184F led to more susceptible isolates to MB (8.0 nM vs. 11.6 nM, p = 0.03). Concerning Pfmdr6, the isolates bearing 12 Asn repetitions were more susceptible to MB (4.6 nM vs. 11.6 nM, p = 0.005). None of the polymorphisms previously described as involved in antimalarial drug resistance was shown to be associated with reduced susceptibility to MB. Some genes (particularly PfK13, Pfugt, Pfact, Pfpm2) did not present enough genetic variability to draw conclusions about their involvement in reduced susceptibility to MB. None of the polymorphisms analyzed by multiple correspondence analysis (MCA) had an impact on the MB susceptibility of the samples successfully included in the analysis. It seems that there is no in vitro cross-resistance between MB and commonly used antimalarial drugs.

In Vitro Susceptibility of Plasmodium falciparum Isolates from Jilore, Kenya, to Antimalarial Drugs

1987 ◽  
Vol 37 (3) ◽  
pp. 445-451 ◽  
Author(s):  
William M. Watkins ◽  
A. David Brandling-Bennett ◽  
David K. Koech ◽  
Robert E. Howells
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Drugs ◽  
In Vitro Susceptibility

scholarly journals Sentinel network for monitoring in vitro susceptibility of Plasmodium falciparum to antimalarial drugs in Colombia: a proof of concept

2011 ◽  
Vol 106 (suppl 1) ◽  
pp. 123-129 ◽  
Author(s):  
Samanda L Aponte ◽  
Gustavo Díaz ◽  
Zuleima Pava ◽  
Diego F Echeverry ◽  
Darío Ibarguen ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Drugs ◽  
Proof Of Concept ◽  
In Vitro Susceptibility ◽  
Sentinel Network

Resistance of Plasmodium falciparum to antimalarial drugs in a highly endemic area of southern Viet Nam: a study in vivo and in vitro

2001 ◽  
Vol 95 (3) ◽  
pp. 325-329 ◽  
Author(s):  
Nguyen Mai Huong ◽  
Sean Hewitt ◽  
Timothy M.E. Davis ◽  
Le Duc Dao ◽  
Tran Quoc Toan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Endemic Area ◽  
Antimalarial Drugs ◽  
Viet Nam

scholarly journals Decreasingpfmdr1Copy Number Suggests that Plasmodium falciparum in Western Cambodia Is RegainingIn VitroSusceptibility to Mefloquine

2015 ◽  
Vol 59 (5) ◽  
pp. 2934-2937 ◽  
Author(s):  
Pharath Lim ◽  
Dalin Dek ◽  
Vorleak Try ◽  
Sokunthea Sreng ◽  
Seila Suon ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Combination Therapy ◽  
Molecular Marker ◽  
Copy Number ◽  
Artemisinin Combination Therapy ◽  
Clinical Isolates ◽  
Content Type

ABSTRACTDihydroartemisinin-piperaquine is the current frontline artemisinin combination therapy (ACT) forPlasmodium falciparummalaria in Cambodia but is now failing in several western provinces. To investigate artesunate plus mefloquine (AS+MQ) as a replacement ACT, we measured the prevalence of multiplepfmdr1copies—a molecular marker for MQ resistance—in 844P. falciparumclinical isolates collected in 2008 to 2013. Thepfmdr1copy number is decreasing in Western Cambodia, suggesting thatP. falciparumis regainingin vitrosusceptibility to MQ.

scholarly journals Role ofPfmdr1inIn VitroPlasmodium falciparum Susceptibility to Chloroquine, Quinine, Monodesethylamodiaquine, Mefloquine, Lumefantrine, and Dihydroartemisinin

2014 ◽  
Vol 58 (12) ◽  
pp. 7032-7040 ◽  
Author(s):  
Nathalie Wurtz ◽  
Bécaye Fall ◽  
Aurélie Pascual ◽  
Mansour Fall ◽  
Eric Baret ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Antimalarial Drug ◽  
Antimalarial Drugs ◽  
Wild Type ◽  
Antimalarial Drug Resistance ◽  
Content Type ◽  
Increased Susceptibility

ABSTRACTThe involvement ofPfmdr1(Plasmodium falciparummultidrug resistance 1) polymorphisms in antimalarial drug resistance is still debated. Here, we evaluate the association between polymorphisms inPfmdr1(N86Y, Y184F, S1034C, N1042D, and D1246Y) andPfcrt(K76T) andin vitroresponses to chloroquine (CQ), mefloquine (MQ), lumefantrine (LMF), quinine (QN), monodesethylamodiaquine (MDAQ), and dihydroartemisinin (DHA) in 174Plasmodium falciparumisolates from Dakar, Senegal. ThePfmdr186Y mutation was identified in 14.9% of the samples, and the 184F mutation was identified in 71.8% of the isolates. No 1034C, 1042N, or 1246Y mutations were detected. ThePfmdr186Y mutation was significantly associated with increased susceptibility to MDAQ (P= 0.0023), LMF (P= 0.0001), DHA (P= 0.0387), and MQ (P= 0.00002). The N86Y mutation was not associated with CQ (P= 0.214) or QN (P= 0.287) responses. ThePfmdr1184F mutation was not associated with various susceptibility responses to the 6 antimalarial drugs (P= 0.168 for CQ, 0.778 for MDAQ, 0.324 for LMF, 0.961 for DHA, 0.084 for QN, and 0.298 for MQ). ThePfmdr186Y-Y184 haplotype was significantly associated with increased susceptibility to MDAQ (P= 0.0136), LMF (P= 0.0019), and MQ (P= 0.0001). The additionalPfmdr186Y mutation increased significantly thein vitrosusceptibility to MDAQ (P< 0.0001), LMF (P< 0.0001), MQ (P< 0.0001), and QN (P= 0.0026) in wild-typePfcrtK76 parasites. The additionalPfmdr186Y mutation significantly increased thein vitrosusceptibility to CQ (P= 0.0179) inPfcrt76T CQ-resistant parasites.

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