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malaria resistance

Raissa Tioyem Nzogong, Fabrice Sterling Tchantchou Ndjateu, Steve Endeguele Ekom, Jules-Arnaud Mboutchom Fosso, Maurice Ducret Awouafack, Mathieu Tene, Pierre Tane, Hiroyuki Morita, Muhammad Iqbal Choudhary, Jean-de-Dieu Tamokou
BACKGROUND: Antimicrobial resistance is a serious threat against humankind and the search for new therapeutics is needed. This study aims to investigate the antimicrobial and antioxidant activities of ethanol extracts and compounds isolated from Dissotis senegambiensis and Amphiblemma monticola, two Cameroonian Melastomataceae species traditionally used for the treatment of fever, malaria and infectious diseases. METHODS: The plant extracts were prepared by maceration in ethanol...
May 16, 2018: BMC Complementary and Alternative Medicine
Thunyapit Thita, Pimrat Jadsri, Jarupatr Thamkhantho, Toon Ruang-Areerate, Nantana Suwandittakul, Naruemon Sitthichot, Kittiya Mahotorn, Peerapan Tan-Ariya, Mathirut Mungthin
BACKGROUND: In Thailand, artemisinin-based combination therapy (ACT) has been used to treat uncomplicated falciparum malaria since 1995. Unfortunately, artemisinin resistance has been reported from Thailand and other Southeast Asian countries since 2003. Malarone® , a combination of atovaquone-proguanil (ATQ-PG), has been used to cease artemisinin pressure in some areas along Thai-Cambodia border, as part of an artemisinin resistance containment project since 2009. This study aimed to determine genotypes and phenotypes of Plasmodium falciparum isolates collected from the Thai-Cambodia border after the artemisinin resistance containment project compared with those collected before...
May 15, 2018: Malaria Journal
Sahil Kumar, T R Bhardwaj, D N Prasad, Rajesh K Singh
New antimalarial targets are the prime need for the discovery of potent drug candidates. In order to fulfill this objective, antimalarial drug researches are focusing on promising targets in order to develop new drug candidates. Basic metabolism and biochemical process in the malaria parasite, i.e. Plasmodium falciparum can play an indispensable role in the identification of these targets. But, the emergence of resistance to antimalarial drugs is an escalating comprehensive problem with the progress of antimalarial drug development...
May 11, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Gerald Mboowa, Ivan Sserwadda, Marion Amujal, Norah Namatovu
HIV/AIDS, tuberculosis (TB), and malaria are 3 major global public health threats that undermine development in many resource-poor settings. Recently, the notion that positive selection during epidemics or longer periods of exposure to common infectious diseases may have had a major effect in modifying the constitution of the human genome is being interrogated at a large scale in many populations around the world. This positive selection from infectious diseases increases power to detect associations in genome-wide association studies (GWASs)...
2018: Canadian Journal of Infectious Diseases & Medical Microbiology
Katherine Cumnock, Avni S Gupta, Michelle Lissner, Victoria Chevee, Nicole M Davis, David S Schneider
Pathologic infections are accompanied by a collection of short-term behavioral perturbations collectively termed sickness behaviors [1, 2]. These include changes in body temperature, reduced eating and drinking, and lethargy and mimic behaviors of animals in torpor and hibernation [1, 3-6]. Sickness behaviors are important, pathogen-specific components of the host response to infection [1, 3, 7-9]. In particular, host anorexia has been shown to be beneficial or detrimental depending on the infection [7, 8]...
May 4, 2018: Current Biology: CB
Vrushali Pathak, Roshan Colah, Kanjaksha Ghosh
Background & objectives: High prevalence of certain polymorphic alleles of erythrocytes in malaria endemic area has been linked to the resistance provided by these alleles against parasitic infestations. Numerous studies undertaken to demonstrate this correlation have generated conflicting results. This study was undertaken to investigate the abilities of various polymorphic erythrocytes to support in vitro growth of Plasmodium falciparum parasites. Methods: In this study under in vitro condition the ability of P...
January 2018: Indian Journal of Medical Research
Fiacre R Agossa, Gil G Padonou, Come Z Koukpo, Jacques Zola-Sahossi, Roseric Azondekon, Osei K Akuoko, Juniace Ahoga, Boris N'dombidje, Bruno Akinro, Arsene Jacques Y H Fassinou, Michel Sezonlin, Martin C Akogbeto
BACKGROUND: Scale-up of the distribution of long-lasting insecticide-treated bed nets and indoor residual spraying with insecticides over the last decade have contributed to the considerable decrease of malaria morbidity and mortality in sub-Saharan Africa. Due to the increasing pyrethroid resistance intensity and the spread of carbamate resistance in Anopheles gambiae (s.s.) mosquitoes and the limited number of insecticides recommended by the WHO for vector control, alternative insecticide formulations for IRS with long-lasting residual activity are required to sustain the gains obtained in most malaria-endemic countries...
May 10, 2018: Parasites & Vectors
Jessica Delhaye, Olivier Glaizot, Philippe Christe
Host susceptibility to parasites is likely to be influenced by intrinsic factors, such as host oxidative status determined by the balance between pro-oxidant production and antioxidant defences. As a result, host oxidative status acts as an environmental factor for parasites and may constrain parasite development. We evaluated the role of host oxidative status on infection dynamics of an avian malarial parasite by providing canaries (Serinus canaria) with an antioxidant supplementation composed of vitamin E (a lipophilic antioxidant) and olive oil, a source of monounsaturated fatty acids...
May 9, 2018: Parasitology Research
David Ruiz-Carrillo, Jianqing Lin, Abbas El Sahili, Meng Wei, Siu Kwan Sze, Peter C F Cheung, Christian Doerig, Julien Lescar
Malaria causes every year over half-a-million deaths. The emergence of parasites resistant to available treatments makes the identification of new targets and their inhibitors an urgent task for the development of novel anti-malaria drugs. Protein kinase CK2 is an evolutionary-conserved eukaryotic serine/threonine protein kinase that in Plasmodium falciparum (PfCK2) has been characterized as a promising target for chemotherapeutic intervention against malaria. Here we report a crystallographic structure of the catalytic domain of PfCK2α (D179S inactive single mutant) in complex with ATP at a resolution of 3...
May 9, 2018: Scientific Reports
Nguyen Ngoc Quang, Marina Chavchich, Chu Xuan Anh, Geoffrey W Birrell, Karin van Breda, Thomas Travers, Kerryn Rowcliffe, Michael D Edstein
The pharmacokinetics (PK) and ex vivo activity (pharmacodynamics [PD]) of two artemisinin combination therapies (ACTs) (artemisinin-piperaquine [ARN-PPQ] [Artequick® ] and artesunate-amodiaquine [ARS-AQ] [Coarsucam™ ]) in healthy Vietnamese volunteers were compared following 3-day courses of the ACTs for the preselection of the drugs for falciparum malaria therapy. For PK analysis, serial plasma samples were collected from two separate groups of 22 volunteers after ACT administration. Of these volunteers, ex vivo activity was assessed in plasma samples from seven volunteers who received both ACTs...
May 7, 2018: American Journal of Tropical Medicine and Hygiene
Wilian Augusto Cortopassi, Tanos Celmar Costa Franca, Antoniana Ursine Krettli
In spite of significant efforts to reduce malaria deaths, this disease still kills around 445,000 people every year. Overcoming drug resistance is one of the main goals of current malaria research programs. This is challenging, since the biology of Plasmodium is not fully understood, requiring the development of advanced models for data analysis in the search for new antimalarials. Areas covered: In this review the authors introduce the importance of computational models to address the challenges of drug discovery, presenting examples of pioneering systems biology approaches in the search for new antimalarial drugs and their role in the future of drug research programs...
May 8, 2018: Expert Opinion on Drug Discovery
Nobutaka Kato, Sandra March, Sangeeta N Bhatia, Matthias Marti
Malaria remains one of the deadliest infectious diseases globally. Available therapeutic agents are already limited in their efficacy, and drug resistance threatens to diminish further our ability to prevent and treat the disease. Despite a renewed effort to identify compounds with antimalarial activity, the drug discovery and development pipeline lacks target diversity and availability of compounds that target liver- and gametocyte-stage parasites. Phenotypic screens are a powerful and valuable tool for identifying new chemical compounds with antimalarial activity...
2018: Methods in Molecular Biology
Mitsuko Ohashi, Michael Amoa-Bosompem, Kofi Dadzie Kwofie, Jefferey Agyapong, Richard Adegle, Maxwell Mamfe Sakyiamah, Frederick Ayertey, Kofi Baffuor-Awuah Owusu, Isaac Tuffour, Philip Atchoglo, Nguyen Huu Tung, Takuhiro Uto, Frederick Aboagye, Alfred Ampomah Appiah, Regina Appiah-Opong, Alexander K Nyarko, William Kofi Anyan, Irene Ayi, Daniel Adjei Boakye, Kwadwo Ansah Koram, Dominic Edoh, Shoji Yamaoka, Yukihiro Shoyama, Nobuo Ohta
Trypanosomiasis, leishmaniasis, and malaria are protozoan infections of public health importance with thousands of new cases recorded annually. Control of these infection(s) with existing chemotherapy is limited by drug toxicity, lengthy parenteral treatment, affordability, and/or the emergence of resistant strains. Medicinal plants on the other hand are used in the treatment of various infectious diseases although their chemical properties are not fully evaluated. In this study, we screened 112 crude extracts from 72 selected Ghanaian medicinal plants for anti-Trypanosoma, anti-Leishmania, and anti-Plasmodium activities in vitro and investigated their mechanisms of action...
May 7, 2018: Phytotherapy Research: PTR
Carlos J Chaccour, Kija Ngha'bi, Gloria Abizanda, Angel Irigoyen Barrio, Azucena Aldaz, Fredros Okumu, Hannah Slater, Jose Luis Del Pozo, Gerry Killeen
BACKGROUND: Mosquitoes that feed on animals can survive and mediate residual transmission of malaria even after most humans have been protected with insecticidal bednets or indoor residual sprays. Ivermectin is a widely-used drug for treating parasites of humans and animals that is also insecticidal, killing mosquitoes that feed on treated subjects. Mass administration of ivermectin to livestock could be particularly useful for tackling residual malaria transmission by zoophagic vectors that evade human-centred approaches...
May 4, 2018: Parasites & Vectors
Nana K Minkah, Carola Schafer, Stefan H I Kappe
Malaria parasite infection continues to inflict extensive morbidity and mortality in resource-poor countries. The insufficiently understood parasite biology, continuously evolving drug resistance and the lack of an effective vaccine necessitate intensive research on human malaria parasites that can inform the development of new intervention tools. Humanized mouse models have been greatly improved over the last decade and enable the direct study of human malaria parasites in vivo in the laboratory. Nevertheless, no small animal model developed so far is capable of maintaining the complete life cycle of Plasmodium parasites that infect humans...
2018: Frontiers in Immunology
Min Zhang, Chengqi Wang, Thomas D Otto, Jenna Oberstaller, Xiangyun Liao, Swamy R Adapa, Kenneth Udenze, Iraad F Bronner, Deborah Casandra, Matthew Mayho, Jacqueline Brown, Suzanne Li, Justin Swanson, Julian C Rayner, Rays H Y Jiang, John H Adams
Severe malaria is caused by the apicomplexan parasite Plasmodium falciparum. Despite decades of research, the distinct biology of these parasites has made it challenging to establish high-throughput genetic approaches to identify and prioritize therapeutic targets. Using transposon mutagenesis of P. falciparum in an approach that exploited its AT-rich genome, we generated more than 38,000 mutants, saturating the genome and defining mutability and fitness costs for over 87% of genes. Of 5399 genes, our study defined 2680 genes as essential for optimal growth of asexual blood stages in vitro...
May 4, 2018: Science
Rebecca C Gilson, Robert J Deissler, Richard F Bihary, William C Condit, Mary E Thompson, D'Arbra Blankenship, Kerry O Grimberg, Robert W Brown, Brian T Grimberg
BACKGROUND: Plasmodium falciparum is the deadliest strain of malaria and the mortality rate is increasing because of pathogen drug resistance. Increasing knowledge of the parasite life cycle and mechanism of infection may provide new models for improved treatment paradigms. This study sought to investigate the paramagnetic nature of the parasite's haemozoin to inhibit parasite viability. RESULTS: Paramagnetic haemozoin crystals, a byproduct of the parasite's haemoglobin digestion, interact with a rotating magnetic field, which prevents their complete formation, causing the accumulation of free haem, which is lethal to the parasites...
May 3, 2018: Malaria Journal
Kimberly E Mace, Paul M Arguin, Kathrine R Tan
PROBLEM/CONDITION: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission...
May 4, 2018: MMWR. Surveillance Summaries: Morbidity and Mortality Weekly Report. Surveillance Summaries
Selina Bopp, Pamela Magistrado, Wesley Wong, Stephen F Schaffner, Angana Mukherjee, Pharath Lim, Mehul Dhorda, Chanaki Amaratunga, Charles J Woodrow, Elizabeth A Ashley, Nicholas J White, Arjen M Dondorp, Rick M Fairhurst, Frederic Ariey, Didier Menard, Dyann F Wirth, Sarah K Volkman
Multidrug resistant Plasmodium falciparum in Southeast Asia endangers regional malaria elimination and threatens to spread to other malaria endemic areas. Understanding mechanisms of piperaquine (PPQ) resistance is crucial for tracking its emergence and spread, and to develop effective strategies for overcoming it. Here we analyze a mechanism of PPQ resistance in Cambodian parasites. Isolates exhibit a bimodal dose-response curve when exposed to PPQ, with the area under the curve quantifying their survival in vitro...
May 2, 2018: Nature Communications
Gediminas Valkiūnas, Mikas Ilgūnas, Dovilė Bukauskaitė, Karin Fragner, Herbert Weissenböck, Carter T Atkinson, Tatjana A Iezhova
BACKGROUND: Microscopic research has shown that Plasmodium relictum is the most common agent of avian malaria. Recent molecular studies confirmed this conclusion and identified several mtDNA lineages, suggesting the existence of significant intra-species genetic variation or cryptic speciation. Most identified lineages have a broad range of hosts and geographical distribution. Here, a rare new lineage of P. relictum was reported and information about biological characters of different lineages of this pathogen was reviewed, suggesting issues for future research...
May 2, 2018: Malaria Journal
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