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https://www.readbyqxmd.com/read/28087668/the-threshold-of-protection-from-liver-stage-malaria-relies-on-a-fine-balance-between-the-number-of-infected-hepatocytes-and-effector-cd8-t-cells-present-in-the-liver
#1
Alexandra J Spencer, Rhea J Longley, Anita Gola, Marta Ulaszewska, Teresa Lambe, Adrian V S Hill
Since the demonstration of sterile protection afforded by injection of irradiated sporozoites, CD8(+) T cells have been shown to play a significant role in protection from liver-stage malaria. This is, however, dependent on the presence of an extremely high number of circulating effector cells, thought to be necessary to scan, locate, and kill infected hepatocytes in the short time that parasites are present in the liver. We used an adoptive transfer model to elucidate the kinetics of the effector CD8(+) T cell response in the liver following Plasmodium berghei sporozoite challenge...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087198/cloning-characterization-and-transmission-blocking-potential-of-midgut-carboxypeptidase-a-in-anopheles-stephensi
#2
V VenkatRao, Surendra K Kumar, P Sridevi, Vijaykumar Muley, R K Chaitanya
Transmission-blocking vaccines (TBV) interrupt malaria parasite transmission and hence form an important component for malaria eradication. Mosquito midgut exopeptidases such as aminopeptidase N & carboxypeptidase B have demonstrated TBV potential. In the present study, we cloned and characterized carboxypeptidase A (CPA) from the midgut of an important malarial vector, Anopheles stephensi. ClustalW amino acid alignment and in silico 3-dimensional structure analysis of CPA predicted the presence of active sites involved in zinc and substrate binding that are conserved among all the known mosquito species...
January 10, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28086789/detection-of-plasmodium-knowlesi-plasmodium-falciparum-and-plasmodium-vivax-using-loop-mediated-isothermal-amplification-lamp-in-a-co-endemic-area-in-malaysia
#3
Kim A Piera, Ammar Aziz, Timothy William, David Bell, Iveth J González, Bridget E Barber, Nicholas M Anstey, Matthew J Grigg
BACKGROUND: Plasmodium knowlesi is the most common cause of malaria in Malaysia. However, microscopic diagnosis is inaccurate and rapid diagnostic tests (RDTs) are insufficiently sensitive. PCR is sensitive and specific but not feasible at a district level. Loop-mediated isothermal amplification (LAMP) shows potential with only basic requirements. A commercially available LAMP assay, the Eiken Loopamp™ MALARIA Pan Detection kit, is sensitive for Plasmodium falciparum and Plasmodium vivax, but has not previously been evaluated for P...
January 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28086782/in-vivo-antiplasmodial-activity-and-toxicological-assessment-of-hydroethanolic-crude-extract-of-ajuga-remota
#4
Aschalew Nardos, Eyasu Makonnen
BACKGROUND: Malaria is one of the most life-threatening health problems worldwide and treatment has been compromised by drug resistance. Identifying lead molecules from natural products might help to find better anti-malarial drugs, since those obtained from natural sources are still effective against malarial parasites. This study aimed at investigating the in vivo antiplasmodial activity of crude extract of the leaves of Ajuga remota together with its safety in mice models. METHODS: In vivo parasite growth inhibitory effect of crude extract was assessed in mice inoculated with Plasmodium berghei (ANKA strain)...
January 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28086775/rapid-decline-in-the-susceptibility-of-plasmodium-falciparum-to-dihydroartemisinin-piperaquine-in-the-south-of-vietnam
#5
Ngo Viet Thanh, Nguyen Thuy-Nhien, Nguyen Thi Kim Tuyen, Nguyen Thanh Tong, Nguyen Thuy Nha-Ca, Le Thanh Dong, Huynh Hong Quang, Jeremy Farrar, Guy Thwaites, Nicholas J White, Marcel Wolbers, Tran Tinh Hien
BACKGROUND: Artemisinin resistant Plasmodium falciparum has emerged in the countries of the Greater Mekong sub-region posing a serious threat to global malaria elimination efforts. The relationship of artemisinin resistance to treatment failure has been unclear. METHODS: In annual studies conducted in three malaria endemic provinces in the south of Vietnam (Binh Phuoc, Ninh Thuan and Gia Lai) between 2011 and 2015, 489 patients with uncomplicated P. falciparum malaria were enrolled in detailed clinical, parasitological and molecular therapeutic response assessments with 42 days follow up...
January 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28081440/a-knockout-screen-of-apiap2-genes-reveals-networks-of-interacting-transcriptional-regulators-controlling-the-plasmodium-life-cycle
#6
Katarzyna Modrzynska, Claudia Pfander, Lia Chappell, Lu Yu, Catherine Suarez, Kirsten Dundas, Ana Rita Gomes, David Goulding, Julian C Rayner, Jyoti Choudhary, Oliver Billker
A family of apicomplexa-specific proteins containing AP2 DNA-binding domains (ApiAP2s) was identified in malaria parasites. This family includes sequence-specific transcription factors that are key regulators of development. However, functions for the majority of ApiAP2 genes remain unknown. Here, a systematic knockout screen in Plasmodium berghei identified ten ApiAP2 genes that were essential for mosquito transmission: four were critical for the formation of infectious ookinetes, and three were required for sporogony...
January 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28081253/probability-of-transmission-of-malaria-from-mosquito-to-human-is-regulated-by-mosquito-parasite-density-in-na%C3%A3-ve-and-vaccinated-hosts
#7
Thomas S Churcher, Robert E Sinden, Nick J Edwards, Ian D Poulton, Thomas W Rampling, Patrick M Brock, Jamie T Griffin, Leanna M Upton, Sara E Zakutansky, Katarzyna A Sala, Fiona Angrisano, Adrian V S Hill, Andrew M Blagborough
Over a century since Ronald Ross discovered that malaria is caused by the bite of an infectious mosquito it is still unclear how the number of parasites injected influences disease transmission. Currently it is assumed that all mosquitoes with salivary gland sporozoites are equally infectious irrespective of the number of parasites they harbour, though this has never been rigorously tested. Here we analyse >1000 experimental infections of humans and mice and demonstrate a dose-dependency for probability of infection and the length of the host pre-patent period...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28081133/the-power-of-malaria-vaccine-trials-using-controlled-human-malaria-infection
#8
Luc E Coffeng, Cornelus C Hermsen, Robert W Sauerwein, Sake J de Vlas
Controlled human malaria infection (CHMI) in healthy human volunteers is an important and powerful tool in clinical malaria vaccine development. However, power calculations are essential to obtain meaningful estimates of protective efficacy, while minimizing the risk of adverse events. To optimize power calculations for CHMI-based malaria vaccine trials, we developed a novel non-linear statistical model for parasite kinetics as measured by qPCR, using data from mosquito-based CHMI experiments in 57 individuals...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28080063/optimization-of-2-anilino-4-amino-substituted-quinazolines-into-potent-antimalarial-agents-with-oral-in-vivo-activity
#9
Paul R Gilson, Cyrus Tan, Kate E Jarman, Kym N Lowes, Joan M Curtis, William Nguyen, Adrian E Di Rago, Hayley E Bullen, Boris Prinz, Sandra Duffy, Jonathan B Baell, Craig A Hutton, Helene Jousset Sabroux, Brendan S Crabb, Vicky M Avery, Alan F Cowman, Brad E Sleebs
Novel antimalarial therapeutics that target multiple stages of the parasites lifecycle are urgently required to tackle the emerging problem of resistance with current drugs. Here we describe the optimization of the 2-anilino quinazoline class as antimalarial agents. The class, identified from publicly available antimalarial screening data, was optimized to generate lead compounds that possess potent antimalarial activity against P. falciparum parasites equivalent to the known antimalarials, chloroquine and mefloquine...
January 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28078947/monitoring-of-plasmodium-infection-in-humans-and-potential-vectors-of-malaria-in-a-newly-emerged-focus-in-southern-iran
#10
Mohsen Kalantari, Zahra Soltani, Mostafa Ebrahimi, Masoud Yousefi, Masoumeh Amin, Ayda Shafiei, Kourosh Azizi
Despite control programs, which aim to eliminate malaria from Iran by 2025, transmission of malaria has not been removed from the country. This study aimed to monitor malaria from asymptomatic parasitaemia and clinical cases from about one year of active case surveillance and potential vectors of malaria in the newly emerged focus of Mamasani and Rostam, southern Iran during 2014-2015. Samples were collected and their DNAs were extracted for Polymerase Chain Reaction (PCR) assay using specific primers for detection of Plasmodium species...
January 12, 2017: Pathogens and Global Health
https://www.readbyqxmd.com/read/28078755/modulation-of-host-cell-sumoylation-facilitates-efficient-development-of-plasmodium-berghei-and-toxoplasma-gondii
#11
Mulaka Maruthi, Dipti Singh, Segireddy Rameswara Reddy, Babu S Mastan, Satish Mishra, Kota Arun Kumar
SUMOylation is a reversible post translational modification of proteins that regulates protein stabilization, nucleocytoplasmic transport and protein-protein interactions. Several viruses and bacteria modulate host SUMOylation machinery for efficient infection. Plasmodium sporozoites are infective forms of malaria parasite that infect hepatocytes and transforms into exoerythrocytic forms (EEFs). Here we show that, during EEF development, the distribution of SUMOylated proteins in host cell nuclei was significantly reduced and expression of the SUMOylation enzymes was downregulated...
January 12, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28077589/trimethoprim-sulfamethoxazole-prophylaxis-during-live-malaria-sporozoite-immunization-induces-long-lived-homologous-and-heterologous-protective-immunity-against-sporozoite-challenge
#12
Charlotte V Hobbs, Charles Anderson, Jillian Neal, Tejram Sahu, Solomon Conteh, Tatiana Voza, Jean Langhorne, William Borkowsky, Patrick E Duffy
Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used in malaria-endemic areas in human immunodeficiency virus (HIV)-infected children and HIV-uninfected, HIV-exposed children as opportunistic infection prophylaxis. Despite the known effects that TMP-SMX has in reducing clinical malaria, its impact on development of malaria-specific immunity in these children remains poorly understood. Using rodent malaria models, we previously showed that TMP-SMX, at prophylactic doses, can arrest liver stage development of malaria parasites and speculated that TMP-SMX prophylaxis during repeated malaria exposures would induce protective long-lived sterile immunity targeting pre-erythrocytic stage parasites in mice...
January 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28077587/malaria-parasitemia-and-parasite-density-in-antiretroviral-treated-hiv-infected-adults-following-discontinuation-of-cotrimoxazole-prophylaxis
#13
Ronald K Ottichilo, Christina S Polyak, Bernard Guyah, Benson Singa, Josphat Nyataya, Krista Yuhas, Grace John-Stewart, John N Waitumbi
BACKGROUND:  Cotrimoxazole (CTX) discontinuation increases malaria incidence in human immunodeficiency virus (HIV)-infected individuals. Rates, quantity, and timing of parasitemia rebound following CTX remain undefined. METHODS:  Serial specimens from a trial of HIV-infected individuals receiving antiretroviral treatment (ART) randomized to continue (the CTX arm) or discontinue (the STOP-CTX arm) were examined for malaria parasites by quantitative reverse transcription polymerase chain reaction (PCR)...
January 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28077167/role-of-anopheles-cellia-rufipes-gough-1910-and-other-local-anophelines-in-human-malaria-transmission-in-the-northern-savannah-of-cameroon-a-cross-sectional-survey
#14
Raymond N Tabue, Parfait Awono-Ambene, Josiane Etang, Jean Atangana, Antonio-Nkondjio C, Jean C Toto, Salomon Patchoke, Rose G F Leke, Etienne Fondjo, Abraham P Mnzava, Tessa B Knox, Alexis Tougordi, Martin J Donnelly, Jude D Bigoga
BACKGROUND: As part of a study to determine the impact of insecticide resistance on the effectiveness of long-lasting insecticide treated nets (LLINs) in the north of Cameroon, the unexpectedly high density and anthropophilic behaviour of Anopheles rufipes lead us to investigate this species bionomics and role in human malaria parasite transmission. METHODS: For four consecutive years (2011-2014), annual cross-sectional sampling of adult mosquitoes was conducted during the peak malaria season (September-October) in three health districts in northern Cameroon...
January 11, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28077149/plasmodium-falciparum-malaria-co-infection-with-tick-borne-relapsing-fever-in-dakar
#15
Mamadou A Diallo, Baidy S Kane, Mouhamadou Ndiaye, Mouhamed Dieng, Khadim Diongue, Aida S Badiane, Mame Cheikh Seck, Daouda Ndiaye
BACKGROUND: West African tick-borne relapsing fever (TBRF) due to Borrelia crocidurae and malaria are co-endemics in Senegal. Although expected to be high, co-infections are rarely reported. A case of falciparum malaria and B. crocidurae co-infection in a patient from Velingara (South of Senegal) is discussed. CASE: A 28 year-old-male patient presented to Aristide Le Dantec Hospital for recurrent fever. He initially presented to a local post health of Pikine (sub-urban of Dakar) and was diagnosed for malaria on the basis of positive malaria rapid diagnostic test (RDT) specific to Plamodium falciparum...
January 11, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28073383/evaluation-of-methylene-blue-pyrimethamine-and-its-combination-on-an-in-vitro-neospora-caninum-model
#16
Luiz Miguel Pereira, Isabel Cristina Vigato-Ferreira, Gabriela DE Luca, Cássia Mariana Bronzon DA Costa, Ana Patrícia Yatsuda
Neospora caninum is an apicomplexan parasite strongly related to reproductive problems in cattle. The neosporosis control is not well established and several fronts are under development, predominantly based on immune protection, immunomodulation and chemotherapy. The use of anti-malarial drugs as therapeutic sources has, in theory, considerable potential for any apicomplexan. Drugs such as methylene blue (MB) and pyrimethamine (Pyr) represent therapeutic options for malaria; thus, their use for neosporosis should be assessed...
January 11, 2017: Parasitology
https://www.readbyqxmd.com/read/28072517/arthropod-innate-immune-systems-and-vector-borne-diseases
#17
Richard H G Baxter, Alicia Contet, Kathryn Krueger
Arthropods, especially ticks and mosquitoes, are the vectors for a number of parasitic and viral human diseases including malaria, sleeping sickness, Dengue and Zika. Yet arthropods show tremendous individual variation in their capacity to transmit disease. A key factor in this capacity is genetically encoded immune factors that counteract infection by the pathogen. Arthropod-specific pattern recognition receptors and protease cascades detect and respond to infection. Proteins such as antimicrobial peptides, thioester-containing proteins, and transglutaminases effect responses such as lysis, phagocytosis, melanization and agglutination...
January 10, 2017: Biochemistry
https://www.readbyqxmd.com/read/28069653/the-molecular-epidemiology-of-pf-k13-mutations-in-senegal-using-targeted-amplicon-deep-sequencing
#18
Eldin Talundzic, Yaye D Ndiaye, Awa B Deme, Christian Olsen, Dhruviben S Patel, Shweta Biliya, Rachel Daniels, Fredrik O Vannberg, Sarah K Volkman, Venkatachalam Udhayakumar, Daouda Ndiaye
The emergence of Plasmodium falciparum (Pf) resistance to artemisinin in Southeast Asia threatens malaria control and elimination activities worldwide. Multiple polymorphisms in the Pf kelch gene found in chromosome 13 (Pfk13) have been associated with artemisinin resistance. Surveillance of potential drug resistance loci within a population that may emerge under increasing drug pressure is an important public health activity. In this context, P. falciparum infections from an observational surveillance study in Senegal were genotyped using targeted amplicon deep sequencing (TADS) for Pfk13 polymorphisms...
January 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28067475/the-chaperonin-tric-forms-an-oligomeric-complex-in-the-malaria-parasite-cytosol
#19
Natalie J Spillman, Josh R Beck, Suresh M Ganesan, Jacquin C Niles, Daniel E Goldberg
The malaria parasite exports numerous proteins into its host red blood cell (RBC). The trafficking of these exported effectors is complex. Proteins are first routed through the secretory system, into the parasitophorous vacuole (PV), a membranous compartment enclosing the parasite. Proteins are then translocated across the PV membrane in a process requiring ATP and unfolding. Once in the RBC compartment the exported proteins are then refolded and further trafficked to their final localizations. Chaperones are important in the unfolding and refolding processes...
January 9, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28067439/the-anopheles-gambiae-transcriptome-a-turning-point-for-malaria-control
#20
REVIEW
A Domingos, R Pinheiro-Silva, J Couto, V do Rosário, J de la Fuente
Mosquitoes are important vectors of several pathogens and thereby contribute to the spread of diseases, with social, economic and public health impacts. Amongst the approximately 450 species of Anopheles, about 60 are recognized as vectors of human malaria, the most important parasitic disease. In Africa, Anopheles gambiae is the main malaria vector mosquito. Current malaria control strategies are largely focused on drugs and vector control measures such as insecticides and bed-nets. Improvement of current, and the development of new, mosquito-targeted malaria control methods rely on a better understanding of mosquito vector biology...
January 9, 2017: Insect Molecular Biology
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