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primaquine falciparum

Muzamil Mahdi Abdel Hamid, Kamala Thriemer, Maha E Elobied, Nouh S Mahgoub, Salah A Boshara, Hassan M H Elsafi, Suhaib A Gumaa, Tassneem Hamid, Hanadi Abdelbagi, Hamid M Basheir, Jutta Marfurt, Ingrid Chen, Roly Gosling, Ric N Price, Benedikt Ley
BACKGROUND: First-line schizontocidal treatment for uncomplicated malaria in the Republic of the Sudan is artesunate (total dose 12 mg/kg) plus Sulphadoxine/pyrimethamine (25/1.25 mg/kg) (AS/SP). Patients with Plasmodium vivax are also treated with 14 days primaquine (total dose 3.5 mg/kg) (PQ). The aim of this study was to assess the efficacy of the national policy. METHODS: Patients above 1 year, with microscopy-confirmed, Plasmodium falciparum and/or P. vivax malaria were treated with AS/SP...
March 16, 2018: Malaria Journal
Jinyoung Lee, Tae Im Kim, Jung-Mi Kang, Hojong Jun, Hương Giang Lê, Thị Lam Thái, Woon-Mok Sohn, Moe Kyaw Myint, Khin Lin, Tong-Soo Kim, Byoung-Kuk Na
BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD; EC deficiency is one of the most common X-linked recessive hereditary disorders in the world. Primaquine (PQ) has been used for radical cure of P. vivax to prevent relapse. Recently, it is also used to reduce P. falciparum gametocyte carriage to block transmission. However, PQ metabolites oxidize hemoglobin and generate excessive reactive oxygen species which can trigger acute hemolytic anemia in malaria patients with inherited G6PD deficiency...
March 16, 2018: BMC Infectious Diseases
Rita Capela, Joana Magalhães, Daniela Miranda, Marta Machado, Margarida Sanches-Vaz, Inês S Albuquerque, Moni Sharma, Jiri Gut, Philip J Rosenthal, Raquel Frade, Maria J Perry, Rui Moreira, Miguel Prudêncio, Francisca Lopes
Hybrid compounds may play a critical role in the context of the malaria eradication agenda, which will benefit from therapeutic tools active against the symptomatic erythrocytic stage of Plasmodium infection, and also capable of eliminating liver stage parasites. To address the need for efficient multistage antiplasmodial compounds, a small library of 1,2,4,5-tetraoxane-8- aminoquinoline hybrids, with the metabolically labile C-5 position of the 8-aminoquinoline moiety blocked with aryl groups, was synthesized and screened for antiplasmodial activity and metabolic stability...
February 19, 2018: European Journal of Medicinal Chemistry
Alassane Dicko, Michelle E Roh, Halimatou Diawara, Almahamoudou Mahamar, Harouna M Soumare, Kjerstin Lanke, John Bradley, Koualy Sanogo, Daouda T Kone, Kalifa Diarra, Sekouba Keita, Djibrilla Issiaka, Sekou F Traore, Charles McCulloch, Will J R Stone, Jimee Hwang, Olaf Müller, Joelle M Brown, Vinay Srinivasan, Chris Drakeley, Roly Gosling, Ingrid Chen, Teun Bousema
BACKGROUND: Primaquine and methylene blue are gametocytocidal compounds that could prevent Plasmodium falciparum transmission to mosquitoes. We aimed to assess the efficacy and safety of primaquine and methylene blue in preventing human to mosquito transmission of P falciparum among glucose-6-phosphate dehydrogenase (G6PD)-normal, gametocytaemic male participants. METHODS: This was a phase 2, single-blind, randomised controlled trial done at the Clinical Research Centre of the Malaria Research and Training Centre (MRTC) of the University of Bamako (Bamako, Mali)...
February 5, 2018: Lancet Infectious Diseases
Jurica Levatić, Kristina Pavić, Ivana Perković, Lidija Uzelac, Katja Ester, Marijeta Kralj, Marcel Kaiser, Matthias Rottmann, Fran Supek, Branka Zorc
Primaquine (PQ) is a commonly used drug that can prevent the transmission of Plasmodium falciparum malaria, however toxicity limits its use. We prepared five groups of PQ derivatives: amides 1a-k, ureas 2a-k, semicarbazides 3a,b, acylsemicarbazides 4a-k and bis-ureas 5a-v, and evaluated them for antimalarial activity in vitro against the erythrocytic stage of P. falciparum NF54. Particular substituents, such as trityl (in 2j and 5r) and methoxybenzhydryl (in 3b and 5v) were associated with a favorable cytotoxicity-to-activity ratio...
January 31, 2018: European Journal of Medicinal Chemistry
Patricia M Graves, Leslie Choi, Hellen Gelband, Paul Garner
BACKGROUND: The 8-aminoquinoline (8AQ) drugs act on Plasmodium falciparum gametocytes, which transmit malaria from infected people to mosquitoes. In 2012, the World Health Organization (WHO) recommended a single dose of 0.25 mg/kg primaquine (PQ) be added to malaria treatment schedules in low-transmission areas or those with artemisinin resistance. This replaced the previous recommendation of 0.75 mg/kg, aiming to reduce haemolysis risk in people with glucose-6-phosphate dehydrogenase deficiency, common in people living in malarious areas...
February 2, 2018: Cochrane Database of Systematic Reviews
Katharine A Collins, Claire Yt Wang, Matthew Adams, Hayley Mitchell, Melanie Rampton, Suzanne Elliott, Isaie J Reuling, Teun Bousema, Robert Sauerwein, Stephan Chalon, Jörg J Möhrle, James S McCarthy
BACKGROUND: Drugs and vaccines that can interrupt the transmission of Plasmodium falciparum will be important for malaria control and elimination. However, models for early clinical evaluation of candidate transmission-blocking interventions are currently unavailable. Here we describe a new model for evaluating malaria transmission from humans to Anopheles mosquitoes using controlled human malaria infection (CHMI). METHODS: Seventeen healthy malaria-naïve volunteers underwent CHMI by intravenous inoculation of P...
February 1, 2018: Journal of Clinical Investigation
André Daher, Dhelio Pereira, Marcus V G Lacerda, Márcia A A Alexandre, Cristiana T Nascimento, Júlio Castro Alves de Lima E Silva, Mauro Tada, Rosilene Ruffato, Ivan Maia, Tereza Cristina Dos Santos, Paola Marchesini, Ana Carolina Santelli, David G Lalloo
BACKGROUND: There is general international agreement that the importance of vivax malaria has been neglected, and there is a need for new treatment approaches in an effort to progress towards control and elimination in Latin America. This open label randomized clinical trial evaluated the efficacy and safety of three treatment regimens using either one of two fixed dose artemisinin-based combinations or chloroquine in combination with a short course of primaquine (7-9 days: total dose 3-4...
January 24, 2018: Malaria Journal
W Robert Taylor, Htee Khu Naw, Kathryn Maitland, Thomas N Williams, Melissa Kapulu, Umberto D'Alessandro, James A Berkley, Philip Bejon, Joseph Okebe, Jane Achan, Alfred Ngwa Amambua, Muna Affara, Davis Nwakanma, Jean-Pierre van Geertruyden, Muhindo Mavoko, Pascal Lutumba, Junior Matangila, Philipe Brasseur, Patrice Piola, Rindra Randremanana, Estrella Lasry, Caterina Fanello, Marie Onyamboko, Birgit Schramm, Zolia Yah, Joel Jones, Rick M Fairhurst, Mahamadou Diakite, Grace Malenga, Malcolm Molyneux, Claude Rwagacondo, Charles Obonyo, Endalamaw Gadisa, Abraham Aseffa, Mores Loolpapit, Marie-Claire Henry, Grant Dorsey, Chandy John, Sodiomon B Sirima, Karen I Barnes, Peter Kremsner, Nicholas P Day, Nicholas J White, Mavuto Mukaka
BACKGROUND: In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. METHODS: Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0...
January 18, 2018: BMC Medicine
Ingrid Chen, Halimatou Diawara, Almahamoudou Mahamar, Koualy Sanogo, Sekouba Keita, Daouda Kone, Kalifa Diarra, Moussa Djimde, Mohamed Keita, Joelle Brown, Michelle E Roh, Jimee Hwang, Helmi Pett, Maxwell Murphy, Mikko Niemi, Bryan Greenhouse, Teun Bousema, Roly Gosling, Alassane Dicko
Background: The World Health Organization recommendation on the use of single low-dose primaquine (SLD-PQ) to reduce Plasmodium falciparum malaria transmission requires more safety data. Methods: We conducted an open-label, non-randomized, dose-adjustment trial of the safety of three single doses of primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient adult males in Mali, followed by an assessment of safety in G6PD-deficient boys ages 11-17 years, and 5-10 years, including G6PD-normal control groups...
January 12, 2018: Journal of Infectious Diseases
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
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
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
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
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
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
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
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
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
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
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