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Subhadip Das, Rebecca Dielschneider, Aaron Chanas-LaRue, James B Johnston, Spencer B Gibson
Lysosomes are the most acidic vesicles within mammalian cells and are promising targets for the treatment of breast cancer, glioblastomas and acute myeloid leukemia (AML). Our previous studies have shown that chronic lymphocytic leukemia (CLL) cells are also sensitive to lysosome disruption and cell death, by siramesine or chemotherapy. In the present study, we screened the antimalarial drugs, mefloquine, atovaquone, primaquine, and tafenoquine, for their effects on lysosome disruption and cytotoxicity in primary CLL cells...
June 7, 2018: Leukemia Research
Cindy S Chu, Aung Pyae Phyo, Khin Maung Lwin, Htun Htun Win, Thida San, Aye Aye Aung, Rattanaporn Raksapraidee, Verena I Carrara, Germana Bancone, James Watson, Kerryn A Moore, Jacher Wiladphaingern, Stéphane Proux, Kanlaya Sriprawat, Markus Winterberg, Phaik Yeong Cheah, Amy L Chue, Joel Tarning, Mallika Imwong, François Nosten, Nicholas J White
Background: Chloroquine has been recommended for Plasmodium vivax infections for >60 years, but resistance is increasing. To guide future therapies, the cumulative benefits of using slowly eliminated (chloroquine) vs rapidly eliminated (artesunate) antimalarials, and the risks and benefits of adding radical cure (primaquine) were assessed in a 3-way randomized comparison conducted on the Thailand-Myanmar border. Methods: Patients with uncomplicated P. vivax malaria were given artesunate (2 mg/kg/day for 5 days), chloroquine (25 mg base/kg over 3 days), or chloroquine-primaquine (0...
June 8, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Bushra Moiz, Ayesha Majeed
Hemoglobin S is known to protect against uncomplicated Plasmodium falciparum malaria. However, there is paucity of the literature regarding interaction of HbS and other malaria species. Usually, P. vivax malaria is a relapsing condition, and without radical cure with primaquine, recurrence may be observed even with hemoglobin S.
June 2018: Clinical Case Reports
Pilar Martín-Dávila, Francesca Norman, Jesus Fortún-Abete, Miguel Píris, Ruben Lovatti, Jose Miguel Rubio, Adolfo Martinez-Pérez, Javier Graus, Gema Ta, Jesus Villarubia, Beatriz Mahillo, Rogelio López-Vélez
A 57-year-old man was admitted with fever and thrombocytopenia one month after renal transplantation. He had never received a blood transfusion or travelled outside Spain. A peripheral blood smear revealed Plasmodium malariae and P. ovale parasites, diagnosis confirmed later by malaria PCR. The donor, from Equatorial Guinea, had negative thick and thin blood smears and rapid malaria antigen test prior to organ donation. Peripheral blood malaria PCR was not performed during donor screening. The second renal recipient and the liver recipient were evaluated and were found to be asymptomatic...
June 4, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Andrew A Lover, Emily Dantzer, Bouasy Hongvanthong, Keobouphaphone Chindavongsa, Susie Welty, Tania Reza, Nimol Khim, Didier Menard, Adam Bennett
BACKGROUND: Lao People Democratic Republic (PDR; Laos), a landlocked country in Southeast Asia, has made important progress in reducing malaria morbidity and mortality in the past 5-6 years, and the northern provinces have very low reported incidence. To support national progress towards elimination, it is critical to verify and understand these changes in disease burden. METHODS: A two-stage cluster cross-sectional survey was conducted in four districts within four northern provinces (Khua, Phongsaly Province; Paktha, Bokeo Province; Nambak, Luang Prabang, and Muang Et, Huaphanh Province)...
June 1, 2018: Malaria Journal
Yoshinori Mitsui, Kentaro Kato
The possible emergence of praziquantel (PZQ)-tolerant and/or resistant schistosomes urgently necessitates the study and development of new antischistosomal drugs as alternatives to PZQ. The aim of the present study was to investigate the capacity of three dyes, namely methylene blue (MB), neutral red (NR) and trypan blue (TB), for the assessment of the in vitro antischistosomal effect of antimalarial drugs on Schistosoma mansoni adult worms. S. mansoni adult worms were incubated in a medium alone for control or supplemented with 10 μg/ml primaquine (PQ), artesunate (AR) and amodiaquine (AQ) for five days...
May 31, 2018: Japanese Journal of Infectious Diseases
Changsheng Deng, Bo Huang, Qi Wang, Wanting Wu, Shaoqin Zheng, Hongying Zhang, Di Li, Danghong Feng, Guoming Li, Linlu Xue, Tao Yang, Fei Tuo, Fouad Mohadji, Xin-Zhuan Su, Qin Xu, Zhibing Wu, Li Lin, Jiuyao Zhou, Hong Yan, Affane Bacar, Kamal Said Abdallah, Rachadi A Kéké, Ahamada Msa Mliva, Moussa Mohamed, Xinhua Wang, Shiguang Huang, Fatihou Oithik, Xiao-Bo Li, Fangli Lu, Michael P Fay, Xiao-Hong Liu, Thomas E Wellems, Jianping Song
Background: Mass drug administration (MDA), with or without low-dose primaquine (PMQLD), is being considered for malaria elimination programs. The potential of PMQLD to block malaria transmission by mosquitoes must be balanced against liabilities of its use. Methods: Artemisinin-piperaquine (AP), with or without PMQLD, was administered in 3 monthly rounds across Anjouan Island, Union of Comoros. Plasmodium falciparum malaria rates, mortality, parasitemias, adverse events, and PfK13 Kelch-propeller gene polymorphisms were evaluated...
April 24, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Elizabeth A Ashley, Aung Pyae Phyo
The last two decades have seen a surge in antimalarial drug development with product development partnerships taking a leading role. Resistance of Plasmodium falciparum to the artemisinin derivatives, piperaquine and mefloquine in Southeast Asia means new antimalarials are needed with some urgency. There are at least 13 agents in clinical development. Most of these are blood schizonticides for the treatment of uncomplicated falciparum malaria, under evaluation either singly or as part of two-drug combinations...
May 25, 2018: Drugs
Şua Sümer, Nazlım Aktuğ Demir, Onur Ural, Gizem Çimen, Emine Yalçınkaya
Malaria is an infectious disease caused by an intracellular parasite, Plasmodium, which is transmitted to humans after the bite of an Anopheles mosquito. This disease has been prevalent for decades. It has caused great epidemics in history and has also delayed social and economic development. It is endemic in the Eastern Mediterranean and Southeastern Anatolia regions of our country. The most common plasmodium in our country is P. vivax. In P. vivax infections, patients should be treated with primaquine to eradicate hypnozoites...
May 21, 2018: Türkiye Parazitolojii Dergisi
Thato Motshoge, Grace Ababio, Larysa Aleksenko, Sajini Souda, Charles Waithaka Muthoga, Naledi Mutukwa, Leabaneng Tawe, Pleasure Ramatlho, Lesego Gabaitiri, Simon Chihanga, Tjantilili Mosweunyane, Shimeles Hamda, Kentse Moakofhi, Davies Ntebela, Elias Peloewetse, Loeto Mazhani, Jeffrey M Pernica, John Read, Isaac K Quaye, Giacomo Maria Paganotti
Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is commonly seen in malaria endemic areas as it is known to confer a selective advantage against malaria. Recently, we reported a high proportion of asymptomatic reservoir of Plasmodium vivax in Botswana, that calls for intervention with primaquine to achieve radical cure of vivax malaria. Considering that individuals with this enzyme deficiency are at risk of haemolysis following primaquine treatment, assessment of the population for the relative frequency of G6PD deficiency is imperative...
May 17, 2018: Infection, Genetics and Evolution
Steven Kho, Benediktus Andries, Jeanne R Poespoprodjo, Robert J Commons, Putu A I Shanti, Enny Kenangalem, Nicholas M Douglas, Julie A Simpson, Paulus Sugiarto, Nicholas M Anstey, Ric N Price
Background: Splenectomy increase the risk of severe and fatal infections, however the risk of Plasmodium vivax malaria is unknown. We quantified the Plasmodium species-specific risks of malaria and other outcomes following splenectomy in patients attending a hospital in Papua, Indonesia. Methods: Records of all patients attending Mitra-Masyarakat Hospital 2004-2013 were reviewed, identifying those who underwent splenectomy. Subsequent risks of specific clinical outcomes within 12 months for splenectomized patients were compared to non-splenectomized patients from their first recorded hospital admission...
May 16, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Christopher Dijanic, Jillian Nickerson, Sunita Shakya, Amanda Dijanic, Marilyn Fabbri
Primaquine (an 8-aminoquinoline malarial therapy) is the only FDA-approved therapy to treat the hypnozoite stage of P. vivax . We think of relapse occurring because of parasitic resistance or poor compliance secondary to drug toxicities. However, in patients with repeated treatment failure, we must consider CYP-450 mutations affecting drug metabolism as an important cause of relapse. A 47-year-old man who travelled to a jungle in Venezuela was diagnosed with P. falciparum and P. vivax in July 2015. He was treated with seven rounds of primaquine-based therapy in the following year, all resulted in relapse without further exposure to endemic areas...
2018: Case Reports in Infectious Diseases
Jordi Landier, Daniel M Parker, Aung Myint Thu, Khin Maung Lwin, Gilles Delmas, François H Nosten
BACKGROUND: Potentially untreatable Plasmodium falciparum malaria threatens the Greater Mekong subregion. A previous series of pilot projects in Myanmar, Laos, Cambodia, and Vietnam suggested that mass drug administration was safe, and when added to provision of early diagnosis and treatment, could reduce the reservoir of P falciparum and interrupts transmission. We examined the effects of a scaled-up programme of this strategy in four townships of eastern Myanmar on the incidence of P falciparum malaria...
May 12, 2018: Lancet
James Watson, Walter R J Taylor, Germana Bancone, Cindy S Chu, Podjanee Jittamala, Nicholas J White
BACKGROUND: The 8-aminoquinoline antimalarials, the only drugs which prevent relapse of vivax and ovale malaria (radical cure), cause dose-dependent oxidant haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Patients with <30% and <70% of normal G6PD activity are not given standard regimens of primaquine and tafenoquine, respectively. Both drugs are currently considered contraindicated in pregnant and lactating women. METHODS: Quantitative G6PD enzyme activity data from 5198 individuals were used to estimate the proportions of heterozygous females who would be ineligible for treatment at the 30% and 70% activity thresholds, and the relationship with the severity of the deficiency...
April 2018: PLoS Neglected Tropical Diseases
Judith Recht, Elizabeth A Ashley, Nicholas J White
Primaquine is the only available antimalarial drug that kills dormant liver stages of Plasmodium vivax and Plasmodium ovale malarias and therefore prevents their relapse ('radical cure'). It is also the only generally available antimalarial that rapidly sterilises mature P. falciparum gametocytes. Radical cure requires extended courses of primaquine (usually 14 days; total dose 3.5-7 mg/kg), whereas transmissibility reduction in falciparum malaria requires a single dose (formerly 0.75 mg/kg, now a single low dose [SLD] of 0...
April 2018: PLoS Neglected Tropical Diseases
Gladwin Muchena, Busisani Dube, Rudo Chikodzore, Jasper Pasipamire, Sivakumaran Murugasampillay, Joseph Mberikunashe
BACKGROUND: Malaria remains a public health problem in Zimbabwe. However, malaria elimination has become a foreseeable prospect with Matabeleland South Province making significant gains towards halting local malaria transmission. This study reviews malaria elimination progress and challenges to date utilizing the World Health Organization's Malaria Programme Review framework. RESULTS: Between 2011 and 2015, malaria incidence was less than one case per 1000 population at risk in all districts save for Beitbridge and Gwanda...
April 3, 2018: Malaria Journal
Christof D Vinnemeier, Thierry Rolling
Malaria incidence is decreasing on a global scale, while the number of imported cases has remained at a high level in Germany. To decrease this number, counselling of travellers to malaria-endemic regions is important. Patients to high risk countries need regular chemoprophylaxis. The alternative of stand-by emergency treatment for travellers to regions with low or medium risk has been met with growing criticism. For the treatment of all malaria cases, artemisinins are a mainstay of treatment. Regular follow-up is warranted to prevent relapses...
April 2018: Deutsche Medizinische Wochenschrift
Ric N Price, Nicholas M Douglas
No abstract text is available yet for this article.
March 24, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Mary Ellen Gilder, Warunee Hanpithakphong, Richard M Hoglund, Joel Tarning, Htun Htun Win, Naw Hilda, Cindy S Chu, Germana Bancone, Verena I Carrara, Pratap Singhasivanon, Nicholas J White, François Nosten, Rose McGready
Background: Primaquine is the only drug providing radical cure of Plasmodium vivax malaria. It is not recommended for breastfeeding women as it causes hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals, and breast milk excretion and thus infant exposure are not known. Methods: Healthy G6PD normal breastfeeding women with previous P.vivax infection and their healthy G6PD normal infants between 28 days and 2 years old were enrolled. Mothers took primaquine 0...
March 24, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Xilong Wu, Yundi Wu, Zhiyong Wang, Lixin Liu, Chengxin Sun, Yongming Chen, Chun Wang
Autophagy is a homeostatic lysosome-dependent metabolic process to eliminate damaged or dysfunctional cellular organelles, which is closely associated with tumor progression. Indocyanine green (ICG) can convert NIR light energy to localized heat for cancer cell and tissue ablation. However, the effect of autophagy modulation on ICG-mediated photothermal therapy remains unknown. In this study, it is found that primaquine (PQ) suppresses autophagy flux at a late stage through the impeding fusion of the autophagosome with the lysosome to form an autophagolysosome, leading to cell apoptosis or necrosis...
March 27, 2018: Advanced Healthcare Materials
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