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Malaria drug resistance

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https://www.readbyqxmd.com/read/28531845/artesunate-and-erythropoietin-synergistically-improve-the-outcome-of-experimental-cerebral-malaria
#1
Yunting Du, Guang Chen, Xuexing Zhang, Chunyun Yu, Yaming Cao, Liwang Cui
Cerebral malaria (CM) is a severe neurological syndrome in humans and the main fatal cause of malaria. In malaria epidemic regions, despite appropriate anti-malarial treatment, 10-20% of deaths still occur during the acute phase. This is largely attributable to poor treatment access, therapeutic complexity and drug resistance; thus, developing additional clinical adjunctive therapies is an urgent necessity. In this study, we investigated the effect of artesunate (AST) and recombinant human erythropoietin (rhEPO) using an experimental cerebral malaria (ECM) model-C57BL/6 mice infected with Plasmodium berghei ANKA (PbA)...
May 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28521791/exploring-the-role-of-socioeconomic-factors-in-the-development-and-spread-of-anti-malarial-drug-resistance-a-qualitative-study
#2
Philip Emeka Anyanwu, John Fulton, Etta Evans, Timothy Paget
BACKGROUND: Malaria remains a global health issue with the burden unevenly distributed to the disadvantage of the developing countries of the world. Poverty contributes to the malaria burden as it has the ability to affect integral aspects of malaria control. There have been renewed efforts in the global malaria control, resulting in reductions in the global malaria burden over the last decade. However, the development of resistance to artemisinin-based combination therapy threatens the sustainability of the present success in malaria control...
May 18, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28511056/elimination-of-schistosoma-mansoni-in-infected-mice-by-slow-release-of-artemisone
#3
Daniel Gold, Mohammed Alian, Avraham Domb, Yara Karawani, Maysa Jbarien, Jacques Chollet, Richard K Haynes, Ho Ning Wong, Viola Buchholz, Andreas Greiner, Jacob Golenser
The current treatment of schistosomiasis is based on the anti-helminthic drug praziquantel (PZQ). PZQ affects only the adult stages of schistosomes. In addition, resistance to PZQ is emerging. We suggest a drug, which could serve as a potential alternative or complement to PZQ, and as a means of treating infections at earlier, pre-granuloma stage. Derivatives of the peroxidic antimalarial drug artemisinin have been indicated as alternatives, because both plasmodia and schistosomes are blood-feeding parasites...
May 4, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28502250/antiplasmodial-dihetarylthioethers-target-the-coenzyme-a-synthesis-pathway-in-plasmodium-falciparum-erythrocytic-stages
#4
Thomas Weidner, Leonardo Lucantoni, Abed Nasereddin, Lutz Preu, Peter G Jones, Ron Dzikowski, Vicky M Avery, Conrad Kunick
BACKGROUND: Malaria is a widespread infectious disease that threatens a large proportion of the population in tropical and subtropical areas. Given the emerging resistance against the current standard anti-malaria chemotherapeutics, the development of alternative drugs is urgently needed. New anti-malarials representing chemotypes unrelated to currently used drugs have an increased potential for displaying novel mechanisms of action and thus exhibit low risk of cross-resistance against established drugs...
May 15, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28500788/unraveling-the-importance-of-the-malaria-parasite-helicases
#5
REVIEW
Renu Tuteja
Malaria is a human parasitic disease caused by infection from Plasmodium species, particularly Plasmodium falciparum. Each year millions of people are infected with malaria and large numbers of deaths result due to this deadly infection. P. falciparum contains 14 chromosomes, nearly 5400 genes and a multistage life cycle in humans and mosquitoes. The control of malaria is still a challenge as the parasite is continuously developing resistance to available anti-malarial drugs and the mosquito vector is developing resistance to insecticides...
May 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28493919/genomic-variation-in-plasmodium-vivax-malaria-reveals-regions-under-selective-pressure
#6
Ernest Diez Benavente, Zoe Ward, Wilson Chan, Fady R Mohareb, Colin J Sutherland, Cally Roper, Susana Campino, Taane G Clark
BACKGROUND: Although Plasmodium vivax contributes to almost half of all malaria cases outside Africa, it has been relatively neglected compared to the more deadly P. falciparum. It is known that P. vivax populations possess high genetic diversity, differing geographically potentially due to different vector species, host genetics and environmental factors. RESULTS: We analysed the high-quality genomic data for 46 P. vivax isolates spanning 10 countries across 4 continents...
2017: PloS One
https://www.readbyqxmd.com/read/28490535/vaccines-to-accelerate-malaria-elimination-and-eventual-eradication
#7
Julie Healer, Alan F Cowman, David C Kaslow, Ashley J Birkett
Remarkable progress has been made in coordinated malaria control efforts with substantial reductions in malaria-associated deaths and morbidity achieved through mass administration of drugs and vector control measures including distribution of long-lasting insecticide-impregnated bednets and indoor residual spraying. However, emerging resistance poses a significant threat to the sustainability of these interventions. In this light, the malaria research community has been charged with the development of a highly efficacious vaccine to complement existing malaria elimination measures...
May 10, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28487425/a-variant-pfcrt-isoform-can-contribute-to-plasmodium-falciparum-resistance-to-the-first-line-partner-drug-piperaquine
#8
Satish K Dhingra, Devasha Redhi, Jill M Combrinck, Tomas Yeo, John Okombo, Philipp P Henrich, Annie N Cowell, Purva Gupta, Matthew L Stegman, Jonathan M Hoke, Roland A Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J Egan, David A Fidock
Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisinin-based combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nuclease-based gene editing, we report that addition of the C101F mutation to the chloroquine (CQ) resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites...
May 9, 2017: MBio
https://www.readbyqxmd.com/read/28480232/artemether-lumefantrine-and-dihydroartemisinin-piperaquine-exert-inverse-selective-pressure-on-plasmodium-falciparum-drug-sensitivity-associated-haplotypes-in-uganda
#9
Aimee R Taylor, Jennifer A Flegg, Chris C Holmes, Philippe J Guérin, Carol H Sibley, Melissa D Conrad, Grant Dorsey, Philip J Rosenthal
BACKGROUND: Altered sensitivity to multiple antimalarial drugs is mediated by polymorphisms in pfmdr1, which encodes the Plasmodium falciparum multidrug resistance transporter. In Africa the N86Y and D1246Y polymorphisms have been shown to be selected by treatment, with artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) selecting for wild-type and mutant alleles, respectively. However, there has been little study of pfmdr1 haplotypes, in part because haplotype analyses are complicated by multiclonal infections...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28479726/anti-plasmodial-and-chloroquine-resistance-suppressive-effects-of-embelin
#10
O I Zaid, R Abd Majid, M S Hasidah, M N Sabariah, K Al-Zihiry, Sattar Rahi, R Basir
BACKGROUND: Emergence of chloroquine (CQ) resistance among different strains of Plasmodium falciparum is the worst catastrophe that has ever perplexed the dedicated efforts to eradicate malaria. This urged the scientists to search for new alternatives or sensitizers to augment its antiplasmodium effect. MATERIALS AND METHOD: In this experiment, the potential of embelin, isolated from Embelia ribes, to inhibit the growth and sensitize CQ action was screened using SYBRE-green-I based drug sensitivity and isobologram assays, respectively...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28473165/unpacking-artemisinin-resistance
#11
REVIEW
Jigang Wang, Chengchao Xu, Zhao-Rong Lun, Steven R Meshnick
Artemisinin and its derivatives, in combination with partner drugs, are currently the most effective treatments for malaria parasite infection. Even though artemisinin has been widely used for decades, its mechanism of action had remained controversial until recently. Artemisinin combination therapies (ACTs) have recently been found to be losing efficacy in Southeast Asia. This 'artemisinin resistance', defined by a delayed parasite clearance time, has been associated with several genetic mutations. As with any other drug resistance phenotype, resistance can best be understood based on its mechanism of action...
May 1, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28467668/oxidative-stress-in-malaria-and-artemisinin-combination-therapy-pros-and-cons
#12
REVIEW
Reginald A Kavishe, Jan B Koenderink, Michael Alifrangis
Artemisinin-based combination therapy (ACT) has been adopted as a strategy to mitigate multidrug resistance to antimalarial monotherapies. ACT combines the rapid and effective but rather short plasma half-life antimalarial action of an artemisinin derivative with a longer acting partner drug. Although the exact mechanisms of action of artemisinins is not well understood, several studies have proposed multiple cellular targets of artemisinins with involvement of reactive oxygen species (ROS). Most of the currently used ACT partner drugs are also known to involve ROS production in their mechanisms of action...
May 3, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28465550/in-vivo-efficacy-of-chloroquine-to-clear-asymptomatic-infections-in-mozambican-adults-a-randomized-placebo-controlled-trial-with-implications-for-elimination-strategies
#13
Beatriz Galatas, Lidia Nhamussua, Baltazar Candrinho, Lurdes Mabote, Pau Cisteró, Himanshu Gupta, Regina Rabinovich, Clara Menéndez, Eusebio Macete, Francisco Saute, Alfredo Mayor, Pedro Alonso, Quique Bassat, Pedro Aide
Recent reports regarding the re-emergence of parasite sensitivity to chloroquine call for a new consideration of this drug as an interesting complementary tool in malaria elimination efforts, given its good safety profile and long half-life. A randomized (2:1), single-blind, placebo-controlled trial was conducted in Manhiça, Mozambique, to assess the in-vivo efficacy of chloroquine to clear plasmodium falciparum (Pf) asymptomatic infections. Primary study endpoint was the rate of adequate and parasitological response (ACPR) to therapy on day 28 (PCR-corrected)...
May 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28464937/seasonal-vaccination-against-malaria-a-potential-use-for-an-imperfect-malaria-vaccine
#14
REVIEW
Brian Greenwood, Alassane Dicko, Issaka Sagara, Issaka Zongo, Halidou Tinto, Matthew Cairns, Irene Kuepfer, Paul Milligan, Jean-Bosco Ouedraogo, Ogobara Doumbo, Daniel Chandramohan
In many parts of the African Sahel and sub-Sahel, where malaria remains a major cause of mortality and morbidity, transmission of the infection is highly seasonal. Seasonal malaria chemoprevention (SMC), which involves administration of a full course of malaria treatment to young children at monthly intervals during the high transmission season, is proving to be an effective malaria control measure in these areas. However, SMC does not provide complete protection and it is demanding to deliver for both families and healthcare givers...
May 2, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28464837/the-correlation-between-malaria-rdt-paracheck-pf-%C3%A2-faint-test-bands-and-microscopy-in-the-diagnosis-of-malaria-in-malawi
#15
Ryoko Makuuchi, Sandy Jere, Nobuchika Hasejima, Thoms Chigeda, January Gausi
BACKGROUND: Faint test bands of Paracheck Pf.® are interpreted as malaria positive according to world health organization (WHO) guideline. However if there are conspicuous number of faint test bands, a performance of Paracheck Pf.® could be influenced depending on whether interpreting faint test bands as malaria positive or negative. Finding out the frequency and accurate interpretation of faint test bands are important to prevent the overdiagnosis and drug resistance. METHODS: A cross-sectional, descriptive study was conducted to find out the frequency of faint test bands and evaluate the performance of Paracheck Pf...
May 2, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28460126/quality-of-artemisinin-based-antimalarial-drugs-marketed-in-nigeria
#16
Oisaemi Izevbekhai, Babatunde Adeagbo, Adeniyi Olagunju, Oluseye Bolaji
Background: Artemisinin combination therapy is first-line therapy for treatment of malaria, which is one of the most significant public health problems in Nigeria. With the increasing level of use of these drugs coupled with the emergence of resistance, there is a need for regular post-market surveillance. Method: Twenty different brands of artesunate-containing antimalarial drugs and 10 brands of artemether-lumefantrine were multi-sourced in the south western part of Nigeria and were subjected to identification, weight uniformity test, and assay using United State pharmacopoeia and International Pharmacopoeia monographs...
February 1, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28460112/baseline-in-vivo-ex-vivo-and-molecular-responses-of-plasmodium-falciparum-to-artemether-and-lumefantrine-in-three-endemic-zones-for-malaria-in-colombia
#17
Samanda Aponte, Ángela Patricia Guerra, Catalina Álvarez-Larrotta, Sindy Durley Bernal, César Restrepo, Camila González, María Fernanda Yasnot, Angélica Knudson-Ospina
Background: Colombia began using artemisinin-based combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in 2006. It is necessary to implement resistance surveillance to antimalarial drugs in order to promptly detect changes in parasite susceptibility. The aim of this study was to establish a susceptibility baseline of P. falciparum to artemether-lumefantrine using three monitoring tools. Methods: Patients with uncomplicated malaria treated with artemether-lumefantrine underwent clinical and parasitological follow-up over 28 days...
February 1, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28460016/physicians-compliance-with-the-national-drug-policy-on-malaria-in-a-tertiary-teaching-hospital-india-from-2010-to-2015-a-mixed-method-study
#18
Soundappan Kathirvel, Jaya Prasad Tripathy, Zaw Myo Tun, Binod Kumar Patro, Tarundeep Singh, Ashish Bhalla, Mahesh Devnani, Ewan Wilkinson
Background: National drug policies are formulated to encourage rational use of drugs and to reduce drug resistance. This study assessed physicians' compliance with the National Drug Policy on Malaria at a tertiary care hospital in north India. Methods: This mixed method study extracted data from adult malaria inpatient records of the hospital from 2010-2015, and assessed drug supply at pharmacies. Physicians' practices and perspectives were explored by in-depth interviews...
February 1, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28454557/longitudinal-genomic-surveillance-of-plasmodium-falciparum-malaria-parasites-reveals-complex-genomic-architecture-of-emerging-artemisinin-resistance
#19
Gustavo C Cerqueira, Ian H Cheeseman, Steve F Schaffner, Shalini Nair, Marina McDew-White, Aung Pyae Phyo, Elizabeth A Ashley, Alexandre Melnikov, Peter Rogov, Bruce W Birren, François Nosten, Timothy J C Anderson, Daniel E Neafsey
BACKGROUND: Artemisinin-based combination therapies are the first line of treatment for Plasmodium falciparum infections worldwide, but artemisinin resistance has risen rapidly in Southeast Asia over the past decade. Mutations in the kelch13 gene have been implicated in this resistance. We used longitudinal genomic surveillance to detect signals in kelch13 and other loci that contribute to artemisinin or partner drug resistance. We retrospectively sequenced the genomes of 194 P. falciparum isolates from five sites in Northwest Thailand, over the period of a rapid increase in the emergence of artemisinin resistance (2001-2014)...
April 28, 2017: Genome Biology
https://www.readbyqxmd.com/read/28454537/increase-in-the-prevalence-of-mutations-associated-with-sulfadoxine-pyrimethamine-resistance-in-plasmodium-falciparum-isolates-collected-from-early-to-late-pregnancy-in-nanoro-burkina-faso
#20
Esmée Ruizendaal, Marc C Tahita, Ronald B Geskus, Inge Versteeg, Susana Scott, Umberto d'Alessandro, Palpouguini Lompo, Karim Derra, Maminata Traore-Coulibaly, Menno D de Jong, Henk D F H Schallig, Halidou Tinto, Petra F Mens
BACKGROUND: Pregnant women are a high-risk group for Plasmodium falciparum infections, which may result in maternal anaemia and low birth weight newborns, among other adverse birth outcomes. Intermittent preventive treatment with sulfadoxine-pyrimethamine during pregnancy (IPTp-SP) is widely implemented to prevent these negative effects of malaria. However, resistance against SP by P. falciparum may decrease efficacy of IPTp-SP. Combinations of point mutations in the dhps (codons A437, K540) and dhfr genes (codons N51, C59, S108) of P...
April 28, 2017: Malaria Journal
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