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Primaquine

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https://www.readbyqxmd.com/read/29042501/plasmodium-falciparum-calcium-dependent-protein-kinase-2-is-critical-for-male-gametocyte-exflagellation-but-not-essential-for-asexual-proliferation
#1
Abhisheka Bansal, Alvaro Molina-Cruz, Joseph Brzostowski, Jianbing Mu, Louis H Miller
Drug development efforts have focused mostly on the asexual blood stages of the malaria parasite Plasmodium falciparum Except for primaquine, which has its own limitations, there are no available drugs that target the transmission of the parasite to mosquitoes. Therefore, there is a need to validate new parasite proteins that can be targeted for blocking transmission. P. falciparum calcium-dependent protein kinases (PfCDPKs) play critical roles at various stages of the parasite life cycle and, importantly, are absent in the human host...
October 17, 2017: MBio
https://www.readbyqxmd.com/read/29020124/glucose-6-phosphate-dehydrogenase-deficiency-and-the-use-of-primaquine-top-down-and-bottom-up-estimation-of-professional-costs
#2
Henry Maia Peixoto, Marcelo Augusto Mota Brito, Gustavo Adolfo Sierra Romero, Wuelton Marcelo Monteiro, Marcus Vinícius Guimarães de Lacerda, Maria Regina Fernandes de Oliveira
The aim of this study has been to study whether the top-down method, based on the average value identified in the Brazilian Hospitalization System (SIH/SUS), is a good estimator of the cost of health professionals per patient, using the bottom-up method for comparison. The study has been developed from the context of hospital care offered to the patient carrier of glucose-6-phosphate dehydrogenase (G6PD) deficiency with severe adverse effect because of the use of primaquine, in the Brazilian Amazon. The top-down method based on the spending with SIH/SUS professional services, as a proxy for this cost, corresponded to R$60...
October 5, 2017: Revista de Saúde Pública
https://www.readbyqxmd.com/read/29016333/distribution-of-mutations-associated-with-antifolate-and-chloroquine-resistance-among-imported-plasmodium-vivax-in-the-state-of-qatar
#3
Devendra Bansal, Anushree Acharya, Praveen K Bharti, Mohamed H Abdelraheem, Ashraf Elmalik, Salem Abosalah, Fahmi Y Khan, Mohamed ElKhalifa, Hargobinder Kaur, Pradyumna K Mohapatra, Rakesh Sehgal, Mohammed A Idris, Jagadish Mahanta, Neeru Singh, Hamza A Babiker, Ali A Sultan
Plasmodium vivax is the most prevalent parasite worldwide, escalating by spread of drug resistance. Currently, in Qatar, chloroquine (CQ) plus primaquine are recommended for the treatment of P. vivax malaria. The present study examined the prevalence of mutations in dihydrofolate reductase (dhfr), dihydropteroate synthase (dhps) genes and CQ resistance transporter (crt-o) genes, associated with sulphadoxine-pyrimethamine (SP) and chloroquine resistance, among imported P. vivax cases in Qatar. Blood samples were collected from patients positive for P...
October 2, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28975866/slco1a2-slco1b1-and-slco2b1-polymorphisms-influences-chloroquine-and-primaquine-treatment-in-plasmodium-vivax-malaria
#4
Vinicius A Sortica, Juliana D Lindenau, Maristela G Cunha, Maria Deise O Ohnishi, Ana Maria R Ventura, Ândrea Kc Ribeiro-Dos-Santos, Sidney Eb Santos, Luciano Sp Guimarães, Mara H Hutz
AIM: The association of transporters gene polymorphisms with chloroquine/primaquine malaria treatment response was investigated in a Brazilian population. PATIENTS & METHODS: Totally, 164 Plasmodium vivax malaria infected patients were included. Generalized estimating equations were performed to determine gene influences on parasitemia and/or gametocytemia clearance over treatment time. RESULTS: Significant interaction between SLCO2B1 genotypes and treatment over time for parasitemia clearance rate on day 2 were observed (p FDR = 0...
October 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28965427/malaria-medicines-to-address-drug-resistance-and-support-malaria-elimination-efforts
#5
Jane Achan, Julia Mwesigwa, Chinagozi Precious Edwin, Umberto D'alessandro
Antimalarial drugs are essential weapons to fight malaria and have been used effectively since the 17(th) century. However, P.falciparum resistance has been reported to almost all available antimalarial drugs, including artemisinin derivatives, raising concerns that this could jeopardize malaria elimination. Areas covered: In this article, we present a historical perspective of antimalarial drug resistance, review current evidence of resistance to available antimalarial drugs and discuss possible mitigating strategies to address this challenge...
October 11, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28954071/a-newly-validated-high-performance-liquid-chromatography-method-with-diode-array-ultraviolet-detection-for-analysis-of-the-antimalarial-drug-primaquine-in-the-blood-plasma
#6
Ana Paula Barbosa do Carmo, Manoella Borborema, Stephan Ribeiro, Ana Cecilia Xavier De-Oliveira, Francisco Jose Roma Paumgartten, Davyson de Lima Moreira
INTRODUCTION: Primaquine (PQ) diphosphate is an 8-aminoquinoline antimalarial drug with unique therapeutic properties. It is the only drug that prevents relapses of Plasmodium vivax or Plasmodium ovale infections. In this study, a fast, sensitive, cost-effective, and robust method for the extraction and high-performance liquid chromatography with diode array ultraviolet detection (HPLC-DAD-UV ) analysis of PQ in the blood plasma was developed and validated. METHODS: After plasma protein precipitation, PQ was obtained by liquid-liquid extraction and analyzed by HPLC-DAD-UV with a modified-silica cyanopropyl column (250mm × 4...
July 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28939120/synthesis-characterization-and-cellular-localization-of-a-fluorescent-probe-of-the-antimalarial-8-aminoquinoline-primaquine
#7
Adonis McQueen, Lynn D Blake, Ala Azhari, M Trent Kemp, Tommy W McGaha, Niranjan Namelikonda, Randy W Larsen, Roman Manetsch, Dennis E Kyle
Primaquine (PQ) is the only commercially available drug that clears dormant liver stages of malaria and blocks transmission to mosquito vectors. Although an old drug, much remains to be known about the mechanism(s) of action. Herein we develop a fluorescent tagged PQ to discover cellular localization in the human malaria parasite, Plasmodium falciparum. Successful synthesis and characterization of a primaquine-coumarin fluorescent probe (PQCP) demonstrated potency equivalent to the parent drug and the probe was not cytotoxic to HepG2 carcinoma cells...
October 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28931236/a-molecular-assay-to-quantify-male-and-female-plasmodium-falciparum-gametocytes-results-from-2-randomized-controlled-trials-using-primaquine-for-gametocyte-clearance
#8
RANDOMIZED CONTROLLED TRIAL
Will Stone, Patrick Sawa, Kjerstin Lanke, Sanna Rijpma, Robin Oriango, Maureen Nyaurah, Paul Osodo, Victor Osoti, Almahamoudou Mahamar, Halimatou Diawara, Rob Woestenenk, Wouter Graumans, Marga van de Vegte-Bolmer, John Bradley, Ingrid Chen, Joelle Brown, Giulia Siciliano, Pietro Alano, Roly Gosling, Alassane Dicko, Chris Drakeley, Teun Bousema
Background: Single low-dose primaquine (PQ) reduces Plasmodium falciparum infectivity before it impacts gametocyte density. Here, we examined the effect of PQ on gametocyte sex ratio as a possible explanation for this early sterilizing effect. Methods: Quantitative reverse-transcription polymerase chain reaction assays were developed to quantify female gametocytes (targeting Pfs25 messenger RNA [mRNA]) and male gametocytes (targeting Pf3D7_1469900 mRNA) in 2 randomized trials in Kenya and Mali, comparing dihydroartemisinin-piperaquine (DP) alone to DP with PQ...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28893237/methods-for-the-field-evaluation-of-quantitative-g6pd-diagnostics-a-review
#9
REVIEW
Benedikt Ley, Germana Bancone, Lorenz von Seidlein, Kamala Thriemer, Jack S Richards, Gonzalo J Domingo, Ric N Price
Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk of severe haemolysis following the administration of 8-aminoquinoline compounds. Primaquine is the only widely available 8-aminoquinoline for the radical cure of Plasmodium vivax. Tafenoquine is under development with the potential to simplify treatment regimens, but point-of-care (PoC) tests will be needed to provide quantitative measurement of G6PD activity prior to its administration. There is currently a lack of appropriate G6PD PoC tests, but a number of new tests are in development and are likely to enter the market in the coming years...
September 11, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28886443/antiplasmodial-activities-of-dyes-against-plasmodium-falciparum-asexual-and-sexual-stages-contrasted-uptakes-of-triarylmethanes-brilliant-green-green-s-e142-and-patent-blue-v-e131-by-erythrocytes
#10
Louis-Jérôme Leba, Jean Popovici, Yannick Estevez, Stéphane Pelleau, Eric Legrand, Lise Musset, Christophe Duplais
The search for safe antimalarial compounds acting against asexual symptom-responsible stages and sexual transmission-responsible forms of Plasmodium species is one of the major challenges in malaria elimination programs. So far, among current drugs approved for human use, only primaquine has transmission-blocking activity. The discovery of small molecules targeting different Plasmodium falciparum life stages remains a priority in antimalarial drug research. In this context, several independent studies have recently reported antiplasmodial and transmission-blocking activities of commonly used stains, dyes and fluorescent probes against P...
August 2, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28883977/management-of-plasmodium-vivax-risk-and-illness-in-travelers
#11
EDITORIAL
J Kevin Baird
Malaria poses an exceptionally complex problem for providers of travel medicine services. Perceived high risk of exposure during travel typically prompts prescribing protective antimalarial drugs. Suppressive chemoprophylactic agents have dominated strategy for that practice for over 70 years. This broad class of therapeutic agents kills parasites after they emerge from the liver and attempt development in red blood cells. The dominance of suppressive chemoprophylaxis in travel medicine stems largely from the view of Plasmodium falciparum as the utmost threat to the patient - these drugs are poorly suited to preventing Plasmodium vivax and Plasmodium ovale due to inactivity against the latent liver stages of these species not produced by P...
2017: Tropical Diseases, Travel Medicine and Vaccines
https://www.readbyqxmd.com/read/28874081/physicochemical-investigation-and-in-vivo-activity-of-anti-malarial-drugs-co-loaded-in-tween-80-niosomes
#12
Miloni Thakkar, Brijesh S
Drugs used for the treatment and prevention of malaria are often plagued by the problem of development of resistance. This has hampered their therapeutic efficiency and rendered them ineffective for monotherapy. However, if re-packaged and combined properly, many of these neglected anti-malarial drugs can possibly find their way back into the treatment regime. The present study evaluates the use of curcumin (CC) and primaquine (PRI) as an anti-malarial combination, packaged within niosomes, in comparison to their respective monotherapy options...
September 5, 2017: Journal of Liposome Research
https://www.readbyqxmd.com/read/28862132/the-complex-relationship-of-exposure-to-new-plasmodium-infections-and-incidence-of-clinical-malaria-in-papua-new-guinea
#13
Natalie E Hofmann, Stephan Karl, Rahel Wampfler, Benson Kiniboro, Albina Teliki, Jonah Iga, Andreea Waltmann, Inoni Betuela, Ingrid Felger, Leanne J Robinson, Ivo Mueller
The molecular force of blood-stage infection (molFOB) is a quantitative surrogate metric for malaria transmission at population level and for exposure at individual level. Relationships between molFOB, parasite prevalence and clinical incidence were assessed in a treatment-to-reinfection cohort, where P.vivax (Pv) hypnozoites were eliminated in half the children by primaquine (PQ). Discounting relapses, children acquired equal numbers of new P. falciparum (Pf) and Pv blood-stage infections/year (Pf-molFOB = 0-18, Pv-molFOB = 0-23) resulting in comparable spatial and temporal patterns in incidence and prevalence of infections...
September 1, 2017: ELife
https://www.readbyqxmd.com/read/28857064/implementation-of-g6pd-testing-and-primaquine-for-p-vivax-radical-cure-operational-perspectives-from-thailand-and-cambodia
#14
Suravadee Kitchakarn, Dysoley Lek, Sea Thol, Chantheasy Hok, Aungkana Saejeng, Rekol Huy, Nipon Chinanonwait, Krongthong Thimasarn, Chansuda Wongsrichanalai
Following progressive success in reducing the burden of malaria over the past two decades, countries of the Asia Pacific are now aiming for elimination of malaria by 2030. Plasmodium falciparum and Plasmodium vivax are the two main malaria species that are endemic in the region. P. vivax is generally perceived to be less severe but will be harder to eliminate, owing partly to its dormant liver stage (known as a hypnozoite) that can cause multiple relapses following an initial clinical episode caused by a mosquito-borne infection...
September 2017: WHO South-East Asia Journal of Public Health
https://www.readbyqxmd.com/read/28852037/the-g6pd-flow-cytometric-assay-is-a-reliable-tool-for-diagnosis-of-g6pd-deficiency-in-women-and-anaemic-subjects
#15
Germana Bancone, Michael Kalnoky, Cindy S Chu, Nongnud Chowwiwat, Maria Kahn, Benoit Malleret, Pornpimon Wilaisrisak, Laurent Rénia, Gonzalo J Domingo, Francois Nosten
Glucose-6-phosphate dehydrogenase (G6PD) activity is essential for redox equilibrium of red blood cells (RBCs) and, when compromised, the RBCs are more susceptible to haemolysis. 8-aminoquinolines (primaquine and tafenoquine) are used for the radical curative treatment of Plasmodium vivax malaria and can cause haemolysis in G6PD deficient subjects. Haemolytic risk is dependent on treatment dose and patient G6PD status but ultimately it correlates with the number of G6PD deficient RBCs. The G6PD spectrophotometric assay reliably identifies deficient subjects but is less reliable in heterozygous females, especially when other blood conditions are present...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28836792/galactose-anchored-gelatin-nanoparticles-for-primaquine-delivery-and-improved-pharmacokinetics-a-biodegradable-and-safe-approach-for-effective-antiplasmodial-activity-against-p-falciparum-3d7-and-in-vivo-hepatocyte-targeting
#16
Hitesh Kumar, Avinash Gothwal, Iliyas Khan, Kartik T Nakhate, Amit Alexander, Ajazuddin, Vineeta Singh, Umesh Gupta
Primaquine phosphate (PQ) is mainly used as a radical cure therapy to eradicate relapse of malaria at the liver stage, which is particularly caused by P. falciparum and P. vivax. In the present study, PQ-loaded galactosylated gelatin nanoparticles (Gel-LA-PQ-NPs) were formulated using a one-step desolvation technique. The mean particle size of Gel-LA-PQ-NPs was found to be 93.48 ± 6.36 nm with a zeta potential of 4.80 ± 0.20 mV having 69.90 ± 1.53% encapsulation efficiency. Electron microscopy demonstrated that the NPs were spherical in shape and uniformly distributed without any cluster formation...
October 2, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28830424/safety-of-primaquine-given-to-people-with-g6pd-deficiency-systematic-review-of-prospective-studies
#17
Olalekan A Uthman, Patricia M Graves, Rachel Saunders, Hellen Gelband, Marty Richardson, Paul Garner
BACKGROUND: Haemolysis risk with single dose or short course primaquine was evaluated in glucose-6-phosphate dehydrogenase (G6PD) deficient people. METHODS: Major electronic databases (to August 2016) were searched for single or short course 8-aminoquinolines (8-AQ) in (1) randomized comparisons against placebo in G6PD deficient people; and (2) observational comparisons in G6PD deficient compared to replete people. Two authors independently assessed eligibility, risk-of-bias, and extracted data...
August 22, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28826608/high-throughput-multiplex-genotyping-directly-from-blood-or-dried-blood-spot-without-dna-extraction-for-the-screening-of-multiple-g6pd-gene-variants-at-risk-for-drug-induced-hemolysis
#18
Xiaoyi Tian, Jun Zhou, Ye Zhao, Zhibin Cheng, Wenqi Song, Yu Sun, Xiaodong Sun, Zhi Zheng
Clinical or epidemiologic screening of single-nucleotide polymorphism markers requires large-scale multiplexed genotyping. Available genotyping tools require DNA extraction and multiplex PCR, which may limit throughput and suffer amplification bias. Herein, a novel genotyping approach has been developed, multiplex extension and ligation-based probe amplification (MELPA), which eliminates DNA extraction and achieves uniform PCR amplification. MELPA lyses blood or dried blood spot and directly captures specific target DNA to 96-well plates using tailed probes...
September 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28820691/field-trial-of-the-carestart-biosensor-analyzer-for-the-determination-of-glucose-6-phosphate-dehydrogenase-activity-in-haiti
#19
Thomas A Weppelmann, Michael E von Fricken, Tara D Wilfong, Elisa Aguenza, Taina T Philippe, Bernard A Okech
Throughout many developing and tropical countries around the world, malaria remains a significant threat to human health. One barrier to malaria elimination is the ability to safely administer primaquine chemotherapy for the radical cure of malaria infections in populations with a high prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency. In the current study, a field trial of the world's first quantitative, point-of-care assay for measuring G6PD activity was conducted in Haiti. The performance of the CareStart Biosensor Analyzer was compared with the gold standard spectrophotometric assay and genotyping of the G6PD allele in schoolchildren (N = 343) from the Ouest Department of Haiti...
August 14, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28814310/modelling-the-benefits-of-long-acting-or-transmission-blocking-drugs-for-reducing-plasmodium-falciparum-transmission-by-case-management-or-by-mass-treatment
#20
Michael T Bretscher, Jamie T Griffin, Azra C Ghani, Lucy C Okell
BACKGROUND: Anti-malarial drugs are an important tool for malaria control and elimination. Alongside their direct benefit in the treatment of disease, drug use has a community-level effect, clearing the reservoir of infection and reducing onward transmission of the parasite. Different compounds potentially have different impacts on transmission-with some providing periods of prolonged chemoprophylaxis whilst others have greater transmission-blocking potential. The aim was to quantify the relative benefit of such properties for transmission reduction to inform target product profiles in the drug development process and choice of first-line anti-malarial treatment in different endemic settings...
August 16, 2017: Malaria Journal
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