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https://www.readbyqxmd.com/read/29324864/safety-of-single-low-dose-primaquine-in-glucose-6-phosphate-dehydrogenase-deficient-falciparum-infected-african-males-two-open-label-randomized-safety-trials
#1
Guido J H Bastiaens, Alfred B Tiono, Joseph Okebe, Helmi E Pett, Sam A Coulibaly, Bronner P Gonçalves, Muna Affara, Alphonse Ouédraogo, Edith C Bougouma, Guillaume S Sanou, Issa Nébié, John Bradley, Kjerstin H W Lanke, Mikko Niemi, Sodiomon B Sirima, Umberto d'Alessandro, Teun Bousema, Chris Drakeley
BACKGROUND: Primaquine (PQ) actively clears mature Plasmodium falciparum gametocytes but in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals can cause hemolysis. We assessed the safety of low-dose PQ in combination with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in G6PDd African males with asymptomatic P. falciparum malaria. METHODS AND FINDINGS: In Burkina Faso, G6PDd adult males were randomized to treatment with AL alone (n = 10) or with PQ at 0...
2018: PloS One
https://www.readbyqxmd.com/read/29321371/assessing-drug-efficacy-against-plasmodium-falciparum-liver-stages-in-vivo
#2
Erika L Flannery, Lander Foquet, Vorada Chuenchob, Matthew Fishbaugher, Zachary Billman, Mary Jane Navarro, William Betz, Tayla M Olsen, Joshua Lee, Nelly Camargo, Thao Nguyen, Carola Schafer, Brandon K Sack, Elizabeth M Wilson, Jessica Saunders, John Bial, Brice Campo, Susan A Charman, Sean C Murphy, Margaret A Phillips, Stefan Hi Kappe, Sebastian A Mikolajczak
Malaria eradication necessitates new tools to fight the evolving and complex Plasmodium pathogens. These tools include prophylactic drugs that eliminate Plasmodium liver stages and consequently prevent clinical disease, decrease transmission, and reduce the propensity for resistance development. Currently, the identification of these drugs relies on in vitro P. falciparum liver stage assays or in vivo causal prophylaxis assays using rodent malaria parasites; there is no method to directly test in vivo liver stage activity of candidate antimalarials against the human malaria-causing parasite P...
January 11, 2018: JCI Insight
https://www.readbyqxmd.com/read/29310655/methylene-blue-induced-morphological-deformations-in-plasmodium-falciparum-gametocytes-implications-for-transmission-blocking
#3
Ishan Wadi, C Radhakrishna Pillai, Anupkumar R Anvikar, Abhinav Sinha, Mahendra Nath, Neena Valecha
BACKGROUND: Malaria remains a global health problem despite availability of effective tools. For malaria elimination, drugs targeting sexual stages of Plasmodium falciparum need to be incorporated in treatment regimen along with schizonticidal drugs to interrupt transmission. Primaquine is recommended as a transmission blocking drug for its effect on mature gametocytes but is not extensively utilized because of associated safety concerns among glucose-6-phosphate dehydrogenase (G6PD) deficient patients...
January 8, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29228132/vivax-malaria-chemoprophylaxis-the-role-of-atovaquone-proguanil-compared-to-other-options
#4
Meltzer Eyal, Galia Rahav, Schwartz Eli
Background: Atovaquone-Proguanil is considered causal prophylaxis (inhibition of liver-stage schizonts) for Plasmodium falciparum, however, its causal prophylactic efficacy for P. vivax is not known. Travelers returning to non-endemic areas, provide a unique opportunity to study P. vivax prophylaxis. Methods: A retrospective observational study. For 11 years Israeli rafters who had traveled to the Omo River in Ethiopia, a highly malaria endemic area, were followed for at least one year after their return...
December 7, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29110709/the-prevalence-incidence-and-prevention-of-plasmodium-falciparum-infections-in-forest-rangers-in-bu-gia-map-national-park-binh-phuoc-province-vietnam-a-pilot-study
#5
Do Hung Son, Nguyen Thuy-Nhien, Lorenz von Seidlein, Truong Le Phuc-Nhi, Ngo Thi Phu, Nguyen Thi Kim Tuyen, Nguyen Huyen Tran, Nguyen Van Dung, Bui Van Quan, Nicholas P J Day, Arjen M Dondorp, Nicholas J White, Guy E Thwaites, Tran Tinh Hien
BACKGROUND: Prophylaxis for high-risk populations, such as forest workers, could be one component for malaria elimination in the Greater Mekong Sub-region. A study was conducted to assess the malaria incidence in forest rangers and the feasibility of malaria prophylaxis for rangers sleeping in forest camps. METHODS: Forest rangers deployed in the Bu Gia Map National Park, Vietnam were invited to participate in the study. Plasmodium infections were cleared using presumptive treatment, irrespective of malaria status, with a 3-day course dihydroartemisinin/piperaquine (DP) and a 14-day course of primaquine...
November 6, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29082022/systematic-review-of-the-clinical-manifestations-of-glucose-6-phosphate-dehydrogenase-deficiency-in-the-greater-mekong-subregion-implications-for-malaria-elimination-and-beyond
#6
Ken Ing Cherng Ong, Hodaka Kosugi, Sophea Thoeun, Hitomi Araki, Moe Moe Thandar, Moritoshi Iwagami, Bouasy Hongvanthong, Paul T Brey, Shigeyuki Kano, Masamine Jimba
INTRODUCTION: To achieve malaria elimination in the Greater Mekong Subregion (GMS) by 2030, proper case management is necessary. 8-aminoquinolines, such as primaquine, are the only available medicines effective in preventing relapse of the hypnozoite stage of Plasmodium vivax, as well as the onward transmission of Plasmodium falciparum. However, primaquine can cause haemolysis in individuals who have glucose-6-phosphate dehydrogenase deficiency (G6PDd). We conducted a systematic review on the reported clinical manifestations of G6PDd to provide a comprehensive overview of the situation in the GMS...
2017: BMJ Global Health
https://www.readbyqxmd.com/read/29065882/frequency-of-g6pd-mediterranean-in-individuals-with-and-without-malaria-in-southern-pakistan
#7
Bushra Moiz, Haroon Muhammad Arshad, Ahmed Raheem, Hasan Hayat, Najia Karim Ghanchi, M Asim Beg
BACKGROUND: Pakistan has an estimated annual burden of 1.5 million malaria cases. The current situation calls for an effective malaria control and eradication programme in this country. Currently, primaquine is an attractive option for eliminating reservoirs of Plasmodium vivax hypnozoites and killing gametocytes of Plasmodium falciparum. However, this drug causes haemolysis in individuals who are glucose-6-phosphate (G6PD) deficient. It is important to map G6PD deficiency and malaria distribution in Pakistan to design an effective malaria eradication regimen...
October 24, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29062913/safety-and-effectiveness-of-mass-drug-administration-to-accelerate-elimination-of-artemisinin-resistant-falciparum-malaria-a-pilot-trial-in-four-villages-of-eastern-myanmar
#8
Jordi Landier, Ladda Kajeechiwa, May Myo Thwin, Daniel M Parker, Victor Chaumeau, Jacher Wiladphaingern, Mallika Imwong, Olivo Miotto, Krittaya Patumrat, Jureeporn Duanguppama, Dominique Cerqueira, Benoit Malleret, Laurent Rénia, Suphak Nosten, Lorenz von Seidlein, Clare Ling, Stéphane Proux, Vincent Corbel, Julie A Simpson, Arjen M Dondorp, Nicholas J White, François H Nosten
Background: Artemisinin and partner drug-resistant falciparum malaria is expanding over the Greater Mekong Sub-region (GMS). Eliminating falciparum malaria in the GMS while drugs still retain enough efficacy could prevent global spread of antimalarial resistance. Eliminating malaria rapidly requires targeting the reservoir of asymptomatic parasite carriers. This pilot trial aimed to evaluate the acceptability, safety, feasibility and effectiveness of mass-drug administration (MDA) in reducing malaria in four villages in Eastern Myanmar...
2017: Wellcome Open Research
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
#9
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/28965427/malaria-medicines-to-address-drug-resistance-and-support-malaria-elimination-efforts
#10
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/28939120/synthesis-characterization-and-cellular-localization-of-a-fluorescent-probe-of-the-antimalarial-8-aminoquinoline-primaquine
#11
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
#12
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/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
#13
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
#14
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/28862132/the-complex-relationship-of-exposure-to-new-plasmodium-infections-and-incidence-of-clinical-malaria-in-papua-new-guinea
#15
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
#16
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/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
#17
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/28814310/modelling-the-benefits-of-long-acting-or-transmission-blocking-drugs-for-reducing-plasmodium-falciparum-transmission-by-case-management-or-by-mass-treatment
#18
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
https://www.readbyqxmd.com/read/28749756/efficacy-of-different-primaquine-regimens-to-control-plasmodium-falciparum-gametocytemia-in-colombia
#19
Maria Arroyo-Arroyo, Eliana Arango, Jaime Carmona-Fonseca, Beatriz Aristizabal, Stephanie Yanow, Amanda Maestre
Treatment against Plasmodium falciparum malaria includes blood schizonticides to clear asexual parasites responsible for disease. The addition of gametocytocidal drugs can eliminate infectious sexual stages with potential for transmission and the World Health Organization recommends a single dose (SD) of primaquine (PQ) to this end. The efficacy of PQ at 0.75 mg/kg to suppress gametocytemia when administered in single or fractionated doses was evaluated. A clinical controlled study with an open-label design was executed; three groups of 20 subjects were studied sequentially...
September 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28733082/effects-of-novel-triple-stage-antimalarial-ionic-liquids-on-lipid-membrane-models
#20
Ricardo Ferraz, Marina Pinheiro, Ana Gomes, Cátia Teixeira, Cristina Prudêncio, Salette Reis, Paula Gomes
Primaquine-based ionic liquids, obtained by acid-base reaction between parent primaquine and cinnamic acids, were recently found as triple-stage antimalarial hits. These ionic compounds displayed significant activity against both liver- and blood-stage Plasmodium parasites, as well as against stage V P. falciparum parasites. Remarkably, blood-stage activity of the ionic liquids against both chloroquine-sensitive (3D7) and resistant (Dd2) P. falciparum strains was clearly superior to those of the respective covalent (amide) analogues and of parent primaquine...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
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