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https://www.readbyqxmd.com/read/27919897/genetic-evidence-for-cytochrome-b-qi-site-inhibition-by-4-1h-quinolone-3-diarylethers-and-antimycin-in-toxoplasma-gondii
#1
P Holland Alday, Igor Bruzual, Aaron Nilsen, Sovitj Pou, Rolf Winter, Choukri Ben Mamoun, Michael K Riscoe, J Stone Doggett
Toxoplasma gondii is an apicomplexan parasite that causes fatal and debilitating brain and eye disease. Endochin-like-quinolones (ELQs) are preclinical compounds that are efficacious against apicomplexan-caused diseases including toxoplasmosis, malaria and babesiosis. Of the ELQs, ELQ-316 has demonstrated the greatest efficacy against acute and chronic experimental toxoplasmosis. Although genetic analyses in other organisms have highlighted the importance of the cytochrome bc1 complex Qi site for ELQ sensitivity, the mechanism of action of ELQs against T...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27919892/significant-divergence-in-sensitivity-to-antimalarial-drugs-between-neighboring-plasmodium-falciparum-populations-along-the-eastern-border-of-myanmar
#2
Weilin Zeng, Yao Bai, Meilian Wang, Zenglei Wang, Shuang Deng, Yonghua Ruan, Shi Feng, Zhaoqing Yang, Liwang Cui
Malaria parasites in different endemic areas display different levels of resistance to antimalarial drugs as the result of varied drug use histories. To provide updated knowledge of drug sensitivities during the malaria elimination phase in Southeast Asia, an epicenter of multidrug resistance, we determined in vitro susceptibilities of culture-adapted Plasmodium falciparum isolates from two eastern border regions (Wa and Kachin) of Myanmar to ten drugs. Despite their close proximity, the Kachin parasites displayed higher IC50 values than the Wa parasites to chloroquine, piperaquine, naphthoquine, mefloquine, quinine, pyrimethamine, pyronaridine, lumefantrine and dihydroartemisinin...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27919256/the-return-of-chloroquine-susceptible-plasmodium-falciparum-malaria-in-zambia
#3
Sydney Mwanza, Sudhaunshu Joshi, Michael Nambozi, Justin Chileshe, Phidelis Malunga, Jean-Bertin Bukasa Kabuya, Sebastian Hachizovu, Christine Manyando, Modest Mulenga, Miriam Laufer
BACKGROUND: Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to malaria control and elimination. The parasite has developed resistance to every anti-malarial drug introduced for wide-scale treatment. However, the spread of resistance may be reversible. Malawi was the first country to discontinue chloroquine use due to widespread resistance. Within a decade of the removal of drug pressure, the molecular marker of chloroquine-resistant malaria had disappeared and the drug was shown to have excellent clinical efficacy...
December 5, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27918946/toxicity-of-ar-curcumene-and-epi-%C3%AE-bisabolol-from-hedychium-larsenii-zingiberaceae-essential-oil-on-malaria-chikungunya-and-japanese-encephalitis-mosquito-vectors
#4
Mashael Marzouq AlShebly, Fatma Saeed AlQahtani, Marimuthu Govindarajan, Kasi Gopinath, Periasamy Vijayan, Giovanni Benelli
Mosquitoes act as vectors of key pathogens and parasites. Plant essential oils have been recognized as important sources of biopesticides, which do not induce resistance and have limited toxic effects on human health and non-target organisms. In this research, we evaluated the larvicidal and oviposition deterrence activity of Hedychium larsenii essential oil (EO) and its major compounds ar-curcumene and epi-β-bisabolol. Both molecules showed high toxicity against early third instars of Anopheles stephensi (LC50=10...
December 2, 2016: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/27917203/population-genomics-diversity-of-plasmodium-falciparum-in-malaria-patients-attending-okelele-health-centre-okelele-ilorin-kwara-state-nigeria
#5
Olatunji Matthew Kolawole, Olugbenga Ayodeji Mokuolu, Yetunde Adeola Olukosi, Tolulope Ololade Oloyede
BACKGROUND: Plasmodium falciparum, the most dangerous malaria parasite species to humans remains an important public health concern in Okelele, a rural community in Ilorin, Kwara State, Nigeria. There is however little information about the genetic diversity of Plasmodium falciparum in Nigeria. OBJECTIVE: To determine the population genomic diversity of Plasmodium falciparum in malaria patients attending Okelele Community Healthcare Centre, Okelele, Ilorin, Kwara State...
September 2016: African Health Sciences
https://www.readbyqxmd.com/read/27914754/antiparasitic-and-disease-modifying-activity-of-nyctanthes-arbor-tristis-linn-in-malaria-an-exploratory-clinical-study
#6
Chhaya S Godse, Prakash S Tathed, Sameer S Talwalkar, Rama A Vaidya, Ashok J Amonkar, Akhil B Vaidya, Ashok D B Vaidya
BACKGROUND: An unceasing threat of drug resistance continuously poses demand for new antimalarial drugs. A scientific assessment of traditionally used antimalarial plants through reverse pharmacology is crucial for a fast track drug discovery. An Ayurvedic plant Nyctanthesarbor-tristis Linn. - (Parijat) had shown antimalarial activity, with a parasite clearance in 76.6% of 120 patients, in an earlier clinical study. OBJECTIVE: To further explore antimalarial potential of the plant through additional objective markers...
November 30, 2016: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/27913644/the-impact-of-established-immunoregulatory-networks-on-vaccine-efficacy-and-the-development-of-immunity-to-malaria
#7
REVIEW
Marcela Montes de Oca, Michael F Good, James S McCarthy, Christian R Engwerda
The development of vaccines to protect against parasites is difficult, in large part due to complex host-parasite interactions that have evolved over millennia. Parasitic factors such as antigenic variation and host factors such as age, transmission intensity, and genetic influences are all thought to contribute to the limited efficacy of parasite vaccines. A developing theme in field studies investigating antiparasitic immunity is the emergence, establishment, and maintenance of immunoregulatory networks that shape the immune responses to new infections, as well as vaccines, thereby influencing disease outcome...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27912985/immunogenicity-and-malaria-transmission-reducing-potency-of-pfs48-45-and-pfs25-encoded-by-dna-vaccines-administered-by-intramuscular-electroporation
#8
Dibyadyuti Datta, Geetha P Bansal, Dietlind L Gerloff, Barry Ellefsen, Drew Hannaman, Nirbhay Kumar
Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV). Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting. However, it has been challenging to produce a fully folded, functionally active Pfs48/45, using various protein expression platforms. In this study, we demonstrate that full-length Pfs48/45 encoded by DNA plasmids is able to induce significant transmission reducing immune responses...
November 29, 2016: Vaccine
https://www.readbyqxmd.com/read/27912876/in-vitro-and-ex-vivo-activity-of-an-azadirachta-indica-a-juss-seed-kernel-extract-on-early-sporogonic-development-of-plasmodium-in-comparison-with-azadirachtin-a-its-most-abundant-constituent
#9
Nisha Dahiya, Giuseppina Chianese, Solomon Mequanente Abay, Orazio Taglialatela-Scafati, Fulvio Esposito, Giulio Lupidi, Massimo Bramucci, Luana Quassinti, George Christophides, Annette Habluetzel, Leonardo Lucantoni
BACKGROUND: NeemAzal(®) (NA) is a quantified extract from seed kernels of neem, Azadirachta indica A.Juss. (Meliaceae), with a wide spectrum of biological properties, classically ascribed to its limonoid content. NA contains several azadirachtins (A to L), azadirachtin A (AzaA) being its main constituent. AzaA has been shown to inhibit microgamete formation of the rodent malaria parasite Plasmodium berghei, and NA was found to completely inhibit the transmission of Plasmodium berghei to Anopheles stephensi mosquitoes when administered to gametocytemic mice at a corresponding AzaA dose of 50mg/kg before exposure to mosquitoes...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27912758/emerging-polymorphisms-in-falciparum-kelch-13-gene-in-northeastern-region-of-india
#10
Neelima Mishra, Ram Suresh Bharti, Prashant Mallick, Om Prakash Singh, Bina Srivastava, Roma Rana, Sobhan Phookan, Hardev Prasad Gupta, Pascal Ringwald, Neena Valecha
BACKGROUND: Recent reports of emergence and spread of artemisinin resistance in the Southeast Asia region, including Myanmar, pose a greater threat to malaria control and elimination in India. Whole genome sequencing studies have associated mutations in the K13 propeller gene (k13), PF3D7_1343700 with artemisinin resistance both in vitro and in vivo. The aim of the present study was to find the k13 gene polymorphisms in Plasmodium falciparum parasites from the three sites in the Northeast region of India, bordering Bangladesh and Myanmar...
December 3, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27911924/plasmodium-yoelii-nigeriensis-n67-is-a-robust-animal-model-to-study-malaria-transmission-by-south-american-anopheline-mosquitoes
#11
Alessandra S Orfano, Ana Paula M Duarte, Alvaro Molina-Cruz, Paulo F Pimenta, Carolina Barillas-Mury
Malaria is endemic in the American continent and the Amazonian rainforest is the region with the highest risk of transmission. However, the lack of suitable experimental models to infect malaria vectors from the Americas has limited the progress to understand the biology of transmission in this region. Anopheles aquasalis, a major vector in coastal areas of South America, was found to be highly refractory to infection with two strains of Plasmodium falciparum (NF54 and 7G8) and with Plasmodium berghei (mouse malaria), even when the microbiota was eliminated with antibiotics and oxidative stress was reduced with uric acid...
2016: PloS One
https://www.readbyqxmd.com/read/27911910/molecular-markers-of-radiation-induced-attenuation-in-intrahepatic-plasmodium-falciparum-parasites
#12
Miranda S Oakley, Nitin Verma, Hong Zheng, Vivek Anantharaman, Kazuyo Takeda, Yamei Gao, Timothy G Myers, Phuong Thao Pham, Babita Mahajan, Nirbhay Kumar, Davison Sangweme, Abhai K Tripathi, Godfree Mlambo, L Aravind, Sanjai Kumar
Experimental immunization with radiation attenuated sporozoites (RAS) and genetically attenuated sporozoites has proved to be a promising approach for malaria vaccine development. However, parasite biomarkers of growth attenuation and enhanced immune protection in response to radiation remain poorly understood. Here, we report on the effect of an attenuating dose of γ-irradiation (15 krad) on the Plasmodium falciparum sporozoite (PfSPZ) ultrastructure by electron microscopy, growth rate of liver stage P. falciparum in liver cell cultures, and genome-wide transcriptional profile of liver stage parasites by microarray...
2016: PloS One
https://www.readbyqxmd.com/read/27911780/selective-sweep-suggests-transcriptional-regulation-may-underlie-plasmodium-vivax-resilience-to-malaria-control-measures-in-cambodia
#13
Christian M Parobek, Jessica T Lin, David L Saunders, Eric J Barnett, Chanthap Lon, Charlotte A Lanteri, Sujata Balasubramanian, Nicholas Brazeau, Derrick K DeConti, Deen L Garba, Steven R Meshnick, Michele D Spring, Char Meng Chuor, Jeffrey A Bailey, Jonathan J Juliano
Cambodia, in which both Plasmodium vivax and Plasmodium falciparum are endemic, has been the focus of numerous malaria-control interventions, resulting in a marked decline in overall malaria incidence. Despite this decline, the number of P vivax cases has actually increased. To understand better the factors underlying this resilience, we compared the genetic responses of the two species to recent selective pressures. We sequenced and studied the genomes of 70 P vivax and 80 P falciparum isolates collected between 2009 and 2013...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27910908/larval-diet-affects-mosquito-development-and-permissiveness-to-plasmodium-infection
#14
Inbar Linenberg, George K Christophides, Mathilde Gendrin
The larval stages of malaria vector mosquitoes develop in water pools, feeding mostly on microorganisms and environmental detritus. Richness in the nutrient supply to larvae influences the development and metabolism of larvae and adults. Here, we investigated the effects of larval diet on the development, microbiota content and permissiveness to Plasmodium of Anopheles coluzzii. We tested three fish diets often used to rear mosquitoes in the laboratory, including two pelleted diets, Dr. Clarke's Pool Pellets and Nishikoi Fish Pellets, and one flaked diet, Tetramin Fish-Flakes...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27907215/cd8-t-cells-induce-fatal-brainstem-pathology-during-cerebral-malaria-via-luminal-antigen-specific-engagement-of-brain-vasculature
#15
Phillip A Swanson, Geoffrey T Hart, Matthew V Russo, Debasis Nayak, Takele Yazew, Mirna Peña, Shahid M Khan, Chris J Janse, Susan K Pierce, Dorian B McGavern
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection that results in thousands of deaths each year, mostly in African children. The in vivo mechanisms underlying this fatal condition are not entirely understood. Using the animal model of experimental cerebral malaria (ECM), we sought mechanistic insights into the pathogenesis of CM. Fatal disease was associated with alterations in tight junction proteins, vascular breakdown in the meninges / parenchyma, edema, and ultimately neuronal cell death in the brainstem, which is consistent with cerebral herniation as a cause of death...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27907019/the-effects-of-transdermally-delivered-oleanolic-acid-on-malaria-parasites-and-blood-glucose-homeostasis-in-p-berghei-infected-male-sprague-dawley-rats
#16
Happiness P Sibiya, Musa V Mabandla, Cephas T Musabayane
The present study investigated the effects of transdermally delivered oleanolic acid (OA) monotherapy and in combination with chloroquine (CHQ) on malaria parasites and glucose homeostasis of P. berghei-infected male Sprague-Dawley rats. Oral glucose test (OGT) responses to OA-pectin patch and CHQ-OA combination matrix patch were monitored in non-infected and infected rats. To evaluate the short-term effects of treatment, percentage parasitaemia, blood glucose, glycogen and plasma insulin were monitored in separate groups of animals treated with either OA-patch monotherapy or CHQ-OA combination pectin patch over a 21-days period...
2016: PloS One
https://www.readbyqxmd.com/read/27906962/population-density-climate-variables-and-poverty-synergistically-structure-spatial-risk-in-urban-malaria-in-india
#17
Mauricio Santos-Vega, Menno J Bouma, Vijay Kohli, Mercedes Pascual
BACKGROUND: The world is rapidly becoming urban with the global population living in cities projected to double by 2050. This increase in urbanization poses new challenges for the spread and control of communicable diseases such as malaria. In particular, urban environments create highly heterogeneous socio-economic and environmental conditions that can affect the transmission of vector-borne diseases dependent on human water storage and waste water management. Interestingly India, as opposed to Africa, harbors a mosquito vector, Anopheles stephensi, which thrives in the man-made environments of cities and acts as the vector for both Plasmodium vivax and Plasmodium falciparum, making the malaria problem a truly urban phenomenon...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27906127/malaria-parasite-celtos-targets-the-inner-leaflet-of-cell-membranes-for-pore-dependent-disruption
#18
John R Jimah, Nichole D Salinas, Monica Sala-Rabanal, Nathaniel G Jones, L David Sibley, Colin G Nichols, Paul H Schlesinger, Niraj H Tolia
Apicomplexan parasites contain a conserved protein CelTOS that, in malaria parasites, is essential for traversal of cells within the mammalian host and arthropod vector. However, the molecular role of CelTOS is unknown because it lacks sequence similarity to proteins of known function. Here, we determined the crystal structure of CelTOS and discovered CelTOS resembles proteins that bind to and disrupt membranes. In contrast to known membrane disruptors, CelTOS has a distinct architecture, specifically binds phosphatidic acid commonly present within the inner leaflet of plasma membranes, and potently disrupts liposomes composed of phosphatidic acid by forming pores...
December 1, 2016: ELife
https://www.readbyqxmd.com/read/27905633/-failure-to-radical-cure-in-plasmodium-vivax-malaria
#19
Julián García, Agustín Seijo, Andrés Benchetrit, Esteban Couto, Sofía Echazarreta, Susana Lloveras, Tomás Orduna
Relapsing Plasmodium vivax malaria is due to activation of dormant intrahepatic parasitic forms known as hypnozoits. Primaquine is the only available drug effective against hypnozoits and, alongside a schizonticidal drug, constitutes the radical treatment of malaria. Failure of radical treatment is frequently attributed to inadequate dosing, poor adherence, or reinfection. However, several cases of radical treatment failure without these factors have been reported, inferring that metabolic properties of the host or tolerance mechanisms of the parasite may be implied...
August 2016: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
https://www.readbyqxmd.com/read/27903741/whole-killed-blood-stage-vaccine-induced-immunity-suppresses-the-development-of-malaria-parasites-in-mosquitoes
#20
Feng Zhu, Taiping Liu, Chenhao Zhao, Xiao Lu, Jian Zhang, Wenyue Xu
As a malaria transmission-blocking vaccine alone does not confer a direct benefit to the recipient, it is necessary to develop a vaccine that not only blocks malaria transmission but also protects vaccinated individuals. In this study we observed that a whole-killed blood-stage vaccine (WKV) not only conferred protection against the blood-stage challenge but also markedly inhibited the transmission of different strains of the malaria parasite. Although the parasitemia is much lower in WKV-immunized mice challenged with malaria parasites, the gametocytemia is comparable between control and immunized mice during the early stages of infection...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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