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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
#1
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
#2
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
#3
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/28797255/barriers-to-routine-g6pd-testing-prior-to-treatment-with-primaquine
#4
Benedikt Ley, Kamala Thriemer, Jessica Jaswal, Eugenie Poirot, Mohammad Shafiul Alam, Ching Swe Phru, Wasif Ali Khan, Lek Dysoley, Gao Qi, Chong Chee Kheong, Ummi Kalthom Shamsudin, Ingrid Chen, Jimee Hwang, Roly Gosling, Ric N Price
BACKGROUND: Primaquine is essential for the radical cure of vivax malaria, however its broad application is hindered by the risk of drug-induced haemolysis in individuals with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. Rapid diagnostic tests capable of diagnosing G6PD deficiency are now available, but these are not used widely. METHODS: A series of qualitative interviews were conducted with policy makers and healthcare providers in four vivax-endemic countries...
August 10, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28782390/treatment-of-pneumocystis-jirovecii-pneumonia-in-hiv-infected-patients-a-review
#5
Yu-Shan Huang, Jen-Jia Yang, Nan-Yao Lee, Guan-Jhou Chen, Wen-Chien Ko, Hsin-Yun Sun, Chien-Ching Hung
Pneumocystis pneumonia is a potentially life-threatening pulmonary infection that occurs in immunocompromised individuals and HIV-infected patients with a low CD4 cell count. Trimethoprim-sulfamethoxazole has been used as the first-line agent for treatment, but mutations within dihydropteroate synthase gene render potential resistance to sulfamide. Despite advances of combination antiretroviral therapy (cART), Pneumocystis pneumonia continues to occur in HIV-infected patients with late presentation for cART or virological and immunological failure after receiving cART...
August 5, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28776226/a-screen-of-pharmaceutical-drugs-for-their-ability-to-cause-short-term-morbidity-and-mortality-in-the-common-bed-bug-cimex-lectularius-l
#6
Johnathan M Sheele, Gale E Ridge, Wenjing Du, Nikhil Mallipeddi, Mayur Vallabhaneni
The common bed bug, Cimex lectularius L., is a hematophagous ectoparasite that preferentially feeds on humans. Pharmaceuticals present in a person's blood may adversely affect C. lectularius when it feeds. We fed >10,000 C. lectularius on blood samples containing more than 400 different drug doses and drug combinations using an in vitro feeding system to determine insect mortality. The majority of drug doses approximated the peak plasma concentration in humans taking those drugs. Twenty-one drugs were found to cause >17% 12-14-day mortality compared to 8...
August 3, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28749773/hemolytic-potential-of-tafenoquine-in-female-volunteers-heterozygous-for-glucose-6-phosphate-dehydrogenase-g6pd-deficiency-g6pd-mahidol-variant-versus-g6pd-normal-volunteers
#7
Ronnatrai Rueangweerayut, Germana Bancone, Emma J Harrell, Andrew P Beelen, Supornchai Kongpatanakul, Jörg J Möhrle, Vicki Rousell, Khadeeja Mohamed, Ammar Qureshi, Sushma Narayan, Nushara Yubon, Ann Miller, François H Nosten, Lucio Luzzatto, Stephan Duparc, Jörg-Peter Kleim, Justin A Green
Tafenoquine is an 8-aminoquinoline under investigation for the prevention of relapse in Plasmodium vivax malaria. This open-label, dose-escalation study assessed quantitatively the hemolytic risk with tafenoquine in female healthy volunteers heterozygous for the Mahidol(487A) glucose-6-phosphate dehydrogenase (G6PD)-deficient variant versus G6PD-normal females, and with reference to primaquine. Six G6PD-heterozygous subjects (G6PD enzyme activity 40-60% of normal) and six G6PD-normal subjects per treatment group received single-dose tafenoquine (100, 200, or 300 mg) or primaquine (15 mg × 14 days)...
July 24, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28749756/efficacy-of-different-primaquine-regimens-to-control-plasmodium-falciparum-gametocytemia-in-colombia
#8
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...
July 24, 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
#9
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...
July 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28732068/effects-of-liver-stage-clearance-by-primaquine-on-gametocyte-carriage-of-plasmodium-vivax-and-p-falciparum
#10
RANDOMIZED CONTROLLED TRIAL
Rahel Wampfler, Natalie E Hofmann, Stephan Karl, Inoni Betuela, Benson Kinboro, Lina Lorry, Mariabeth Silkey, Leanne J Robinson, Ivo Mueller, Ingrid Felger
BACKGROUND: Primaquine (PQ) is the only currently licensed antimalarial that prevents Plasmodium vivax (Pv) relapses. It also clears mature P. falciparum (Pf) gametocytes, thereby reducing post-treatment transmission. Randomized PQ treatment in a treatment-to-reinfection cohort in Papua New Guinean children permitted the study of Pv and Pf gametocyte carriage after radical cure and to investigate the contribution of Pv relapses. METHODS: Children received radical cure with Chloroquine, Artemether-Lumefantrine plus either PQ or placebo...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28695570/population-pharmacokinetics-and-electrocardiographic-effects-of-dihydroartemisinin-piperaquine-in-healthy-volunteers
#11
Palang Chotsiri, Thanaporn Wattanakul, Richard Hoglund, Borimas Hanboonkunupakarn, Sasithon Pukrittayakamee, Daniel Blessborn, Podjanee Jittamala, Nicholas J White, Nicholas P J Day, Joel Tarning
AIMS: The aims of the presented study were to evaluate the pharmacokinetic properties of dihydroartemisinin and piperaquine, potential drug-drug interactions with concomitant primaquine treatment, and piperaquine effects on the electrocardiogram in healthy volunteers. METHODS: Population pharmacokinetic properties of dihydroartemisinin and piperaquine were assessed in 16 in healthy Thai adults using an open-label randomized crossover study. Drug concentration-time data and electrocardiographic measurements were evaluated with nonlinear mixed-effects modelling...
July 11, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28693488/donor-support-for-quality-assurance-and-pharmacovigilance-of-anti-malarials-in-malaria-endemic-countries
#12
Stephanie D Kovacs, Brianna M Mills, Andy Stergachis
BACKGROUND: Malaria control efforts have been strengthened by funding from donor groups and government agencies. The Global Fund to Fight AIDS, Tuberculosis and the Malaria (Global Fund), the US President's Malaria Initiative (PMI) account for the majority of donor support for malaria control and prevention efforts. Pharmacovigilance (PV), which encompasses all activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problem, is a necessary part of efforts to reduce drug resistance and improve treatment outcomes...
July 11, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28676055/malaria-in-brazil-colombia-peru-and-venezuela-current-challenges-in-malaria-control-and-elimination
#13
REVIEW
Judith Recht, André M Siqueira, Wuelton M Monteiro, Sonia M Herrera, Sócrates Herrera, Marcus V G Lacerda
In spite of significant progress towards malaria control and elimination achieved in South America in the 2000s, this mosquito-transmitted tropical disease remains an important public health concern in the region. Most malaria cases in South America come from Amazon rain forest areas in northern countries, where more than half of malaria is caused by Plasmodium vivax, while Plasmodium falciparum malaria incidence has decreased in recent years. This review discusses current malaria data, policies and challenges in four South American Amazon countries: Brazil, Colombia, Peru and the Bolivarian Republic of Venezuela...
July 4, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28666481/genetic-diversity-and-natural-selection-of-plasmodium-vivax-multi-drug-resistant-gene-pvmdr1-in-mesoamerica
#14
Lilia González-Cerón, Alberto Montoya, Josselin C Corzo-Gómez, Rene Cerritos, Frida Santillán, Marco A Sandoval
BACKGROUND: The Plasmodium vivax multidrug resistant 1 gene (pvmdr1) codes for a transmembrane protein of the parasite's digestive vacuole. It is likely that the pvmdr1 gene mutations occur at different sites by convergent evolution. In here, the genetic variation of pvmdr1 at three sites of the Mesoamerican region was studied. Since 1950s, malarious patients of those areas have been treated only with chloroquine and primaquine. METHODS: Blood samples from patients infected with P...
July 1, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28652237/the-candidate-antimalarial-drug-mmv665909-causes-oxygen-dependent-mrna-mistranslation-and-synergises-with-quinoline-derived-antimalarials
#15
Cindy Vallières, Simon V Avery
To cope with growing resistance to current antimalarials, new drugs with novel modes of action are urgently needed. Molecules targeting protein synthesis appear to be promising candidates. We identified a compound (MMV665909) from the MMV Malaria Box of candidate antimalarials that could produce synergistic growth inhibition with the aminoglycoside antibiotic paromomycin, suggesting a possible action of the compound in mRNA mistranslation. This mechanism of action was substantiated with the yeast cell model using available reporters of mistranslation and other genetic tools...
June 26, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28650618/solution-and-solid-state-correlations-of-antimalarial-drug-actions-nmr-and-crystallographic-studies-of-drug-interactions-with-a-heme-model
#16
Erin L Dodd, Dagobert Tazoo, D Scott Bohle
Solution NMR has been used in tandem with a diamagnetic non-iron heme model compound as a simple and effective tool to rapidly probe the structures of the bound complexes formed between the metalloporphyrin and antimalarial drugs from the 4-aminoquinoline, 4-methylenehydroxylquinoline, and 8-aminoquinoline subfamilies. The ability of gallium(III) protoporphyrin IX to mimic heme chemistry is exploited. The 4-aminoquinolines quinacrine and amodiaquine and two novel 3-halo chloroquine analogues are found to bind to the metalloporphyrin through hydrogen-bonding and stacking interactions, while halofantrine and the 4-methylenehydroxylquinolines, quinine and mefloquine bind through the alcohol group of the drug...
July 17, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28630942/antimalarial-drugs-and-the-prevalence-of-mental-and-neurological-manifestations-a-systematic-review-and-meta-analysis
#17
Mary A Bitta, Symon M Kariuki, Clifford Mwita, Samson Gwer, Leah Mwai, Charles R J C Newton
Background: Antimalarial drugs affect the central nervous system, but it is difficult to differentiate the effect of these drugs from that of the malaria illness. We conducted a systematic review to determine the association between anti-malarial drugs and mental and neurological impairment in humans.  Methods: We systematically searched online databases, including Medline/PubMed, PsychoInfo, and Embase, for articles published up to 14th July 2016. Pooled prevalence, heterogeneity and factors associated with prevalence of mental and neurological manifestations were determined using meta-analytic techniques...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28619120/g6pd-deficiency-alleles-in-a-malaria-endemic-region-in-the-western-brazilian-amazon
#18
Jamille G Dombrowski, Rodrigo M Souza, Jonathan Curry, Laura Hinton, Natercia R M Silva, Lynn Grignard, Ligia A Gonçalves, Ana Rita Gomes, Sabrina Epiphanio, Chris Drakeley, Jim Huggett, Taane G Clark, Susana Campino, Claudio R F Marinho
BACKGROUND: Plasmodium vivax parasites are the predominant cause of malaria infections in the Brazilian Amazon. Infected individuals are treated with primaquine, which can induce haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals and may lead to severe and fatal complications. This X-linked disorder is distributed globally and is caused by allelic variants with a geographical distribution that closely reflects populations exposed historically to endemic malaria...
June 15, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28606284/-efficacy-of-clindamycin-primaquine-as-the-salvage-treatment-for-pneumocystis-pneumonia-in-non-hiv-infected-patients
#19
X Wang, G F Wang, Z Jin, J J Huang, X D Mu, W Zhang
Objective: To evaluate the efficacy of clindamycin-primaquine as the salvage treatment for pneumocystis pneumonia (PCP) in non-HIV-infected patients. Methods: Clinical data of non-HIV-infected patients with PCP who were treated with clindamycin-primaquine as the salvage treatment in Peking University First Hospital from Jan 2010 to May 2016 were collected and reviewed in this retrospective study. Clinical outcomes were analyzed to evaluate the efficacy of clindamycin-primaquine as a salvage treatment. Results: A total of 19 non-HIV-infected patients with PCP were included...
June 13, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28605472/safety-and-efficacy-of-adding-a-single-low-dose-of-primaquine-to-the-treatment-of-adult-patients-with-plasmodium-falciparum-malaria-in-senegal-to-reduce-gametocyte-carriage-a-randomized-controlled-trial
#20
Roger C Tine, Khadime Sylla, Babacar T Faye, Eugenie Poirot, Fatou B Fall, Doudou Sow, Duolao Wang, Magatte Ndiaye, Jean Louis Ndiaye, Babacar Faye, Brian Greenwood, Oumar Gaye, Paul Milligan
Introduction.: More information is needed about the safety of low-dose primaquine in populations where G6PD deficiency is common. Methods.: Adults with Plasmodium falciparum malaria were randomized to receive 1 of 3 artemisinin combination therapies (ACTs) with or without primaquine (0.25 mg/kg). Glucose-6-phosphate dehydrogenase (G6PD) status was determined using a rapid test. Patients were followed for 28 days to record hemoglobin concentration, adverse events, and gametocyte carriage...
June 12, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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