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vivax human challenge

Catarina Bourgard, Letusa Albrecht, Ana C A V Kayano, Per Sunnerhagen, Fabio T M Costa
During the last decade, the vast omics field has revolutionized biological research, especially the genomics, transcriptomics and proteomics branches, as technological tools become available to the field researcher and allow difficult question-driven studies to be addressed. Parasitology has greatly benefited from next generation sequencing (NGS) projects, which have resulted in a broadened comprehension of basic parasite molecular biology, ecology and epidemiology. Malariology is one example where application of this technology has greatly contributed to a better understanding of Plasmodium spp...
2018: Frontiers in Cellular and Infection Microbiology
Kasturi Haldar, Souvik Bhattacharjee, Innocent Safeukui
A marked decrease in malaria-related deaths worldwide has been attributed to the administration of effective antimalarials against Plasmodium falciparum, in particular, artemisinin-based combination therapies (ACTs). Increasingly, ACTs are also used to treat Plasmodium vivax, the second major human malaria parasite. However, resistance to frontline artemisinins and partner drugs is now causing the failure of P. falciparum ACTs in southeast Asia. In this Review, we discuss our current knowledge of markers and mechanisms of resistance to artemisinins and ACTs...
March 2018: Nature Reviews. Microbiology
Tarsila Mendes de Camargo, Elisângela Oliveira de Freitas, Alba Marina Gimenez, Luciana Chagas Lima, Karina de Almeida Caramico, Kátia Sanches Françoso, Oscar Bruna-Romero, Chiara Andolina, François Nosten, Laurent Rénia, Hildegund C J Ertl, Ruth S Nussenzweig, Victor Nussenzweig, Mauricio M Rodrigues, Arturo Reyes-Sandoval, Irene S Soares
Vaccine development against Plasmodium vivax malaria lags behind that for Plasmodium falciparum. To narrow this gap, we administered recombinant antigens based on P. vivax circumsporozoite protein (CSP) to mice. We expressed in Pichia pastoris two chimeric proteins by merging the three central repeat regions of different CSP alleles (VK210, VK247, and P. vivax-like). The first construct (yPvCSP-AllFL) contained the fused repeat regions flanked by N- and C-terminal regions. The second construct (yPvCSP-AllCT) contained the fused repeat regions and the C-terminal domain, plus RI region...
January 18, 2018: Scientific Reports
Pedro Cravo, Renato B Machado, Juliana A Leite, Taizy Leda, Rossarin Suwanarusk, Najara Bittencourt, Letusa Albrecht, Carla Judice, Stefanie C P Lopes, Marcus V G Lacerda, Marcelo U Ferreira, Irene S Soares, Yun Shan Goh, Daniel Y Bargieri, François Nosten, Bruce Russell, Laurent Rénia, Fabio T M Costa
BACKGROUND: Technical limitations for culturing the human malaria parasite Plasmodium vivax have impaired the discovery of vaccine candidates, challenging the malaria eradication agenda. The immunogenicity of the M2 domain of the Merozoite Adhesive Erythrocytic Binding Protein (MAEBL) antigen cloned from the Plasmodium yoelii murine parasite, has been previously demonstrated. RESULTS: Detailed epitope mapping of MAEBL through immunoinformatics identified several MHCI, MHCII and B cell epitopes throughout the peptide, with several of these lying in the M2 domain and being conserved between P...
January 10, 2018: Malaria Journal
Rajeev K Mehlotra, D'Arbra Blankenship, Rosalind E Howes, Tovonahary A Rakotomanga, Brune Ramiranirina, Stephanie Ramboarina, Thierry Franchard, Marlin H Linger, Melinda Zikursh-Blood, Arsène C Ratsimbasoa, Peter A Zimmerman, Brian T Grimberg
BACKGROUND: Plasmodium vivax is the most prevalent human malaria parasite and is likely to increase proportionally as malaria control efforts more rapidly impact the prevalence of Plasmodium falciparum. Despite the prominence of P. vivax as a major human pathogen, vivax malaria qualifies as a neglected and under-studied tropical disease. Significant challenges bringing P. vivax into the laboratory, particularly the capacity for long-term propagation of well-characterized strains, have limited the study of this parasite's red blood cell (RBC) invasion mechanism, blood-stage development, gene expression, and genetic manipulation...
November 3, 2017: Malaria Journal
Anne-Sophie De Koninck, Lieselotte Cnops, Mattias Hofmans, Jan Jacobs, Dorien Van den Bossche, Jan Philippé
BACKGROUND: Light microscopy and antigen-based rapid diagnostic tests are the primary diagnostic tools for detecting malaria, although being labour-intensive and frequently challenged by lack of personnel's experience and low levels of parasite density. The latter being especially important in non-endemic settings. Novel molecular techniques aim to overcome this drawback. The objective of this study was to assess the diagnostic performance of the illumigene malaria assay(®) (Meridian Bioscience) compared to microscopy, RDT and real-time PCR...
October 17, 2017: Malaria Journal
Roberto R Moraes Barros, Tyler J Gibson, Whitney A Kite, Juliana M Sá, Thomas E Wellems
Human infections from Plasmodium knowlesi present challenges to malaria control in Southeast Asia. P. knowlesi also offers a model for other human malaria species including Plasmodium vivax. P. knowlesi parasites can be cultivated in the laboratory, and their transformation is standardly performed by direct electroporation of schizont-infected red blood cells (RBCs) with plasmid DNA. Here we show that the efficiency of direct electroporation is exquisitely dependent on developmental age of the schizonts. Additionally, we show that transformation of P...
December 2017: Molecular and Biochemical Parasitology
Alexander Nissen, Jackie Cook, Eskindir Loha, Bernt Lindtjørn
BACKGROUND: Despite falling incidence and mortality since the turn of the century, malaria remains an important global health challenge. In the future fight against malaria, greater emphasis will have to be placed on understanding and addressing malaria caused by the Plasmodium vivax parasite. Unfortunately, due to years of neglect and underfunding, there are currently many gaps in knowledge of P. vivax malaria. The aims of the present study were to explore the association between distance to vector breeding site and P...
September 19, 2017: Malaria Journal
Danielle I Stanisic, James S McCarthy, Michael F Good
Controlled human malaria infection (CHMI) entails deliberate infection with malaria parasites either by mosquito bite or by direct injection of sporozoites or parasitized erythrocytes. When required, the resulting blood-stage infection is curtailed by the administration of antimalarial drugs. Inducing a malaria infection via inoculation with infected blood was first used as a treatment (malariotherapy) for neurosyphilis in Europe and the United States in the early 1900s. More recently, CHMI has been applied to the fields of malaria vaccine and drug development, where it is used to evaluate products in well-controlled early-phase proof-of-concept clinical studies, thus facilitating progression of only the most promising candidates for further evaluation in areas where malaria is endemic...
January 2018: Infection and Immunity
Ingfar Soontarawirat, Chiara Andolina, Richard Paul, Nicholas P J Day, Francois Nosten, Charles J Woodrow, Mallika Imwong
BACKGROUND: Polyclonal blood-stage infections of Plasmodium vivax are frequent even in low transmission settings, allowing meiotic recombination between heterologous parasites. Empirical data on meiotic products are however lacking. This study examined microsatellites in oocysts derived by membrane feeding of mosquitoes from blood-stage P. vivax infections at the Thai-Myanmar border. METHODS: Blood samples from patients presenting with vivax malaria were fed to Anopheles cracens by membrane feeding and individual oocysts from midguts were obtained by dissection after 7 days...
September 5, 2017: Malaria Journal
Gustavo Cabral-Miranda, Matthew D Heath, Mona O Mohsen, Ariane C Gomes, Paul Engeroff, Amy Flaxman, Fabiana M S Leoratti, Aadil El-Turabi, Arturo Reyes-Sandoval, Murray A Skinner, Matthias F Kramer, Martin F Bachmann
Vaccination is the most effective prophylactic tool against infectious diseases. Despite continued efforts to control malaria, the disease still generally represents a significant unmet medical need. Microcrystalline tyrosine (MCT) is a well described depot used in licensed allergy immunotherapy products and in clinical development. However, its proof of concept in prophylactic vaccines has only recently been explored. MCT has never been used in combination with virus-like particles (VLPs), which are considered to be one of the most potent inducers of cellular and humoral immune responses in mice and humans...
May 2, 2017: Vaccines
Ahmed M Salman, Eduardo Montoya-Díaz, Heather West, Amar Lall, Erwan Atcheson, Cesar Lopez-Camacho, Jai Ramesar, Karolis Bauza, Katharine A Collins, Florian Brod, Fernando Reis, Leontios Pappas, Lilia González-Cerón, Chris J Janse, Adrian V S Hill, Shahid M Khan, Arturo Reyes-Sandoval
Development of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy and support further clinical trials. In this study, we report the development of a highly protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21, able to provide 100% sterile protection against a stringent sporozoite challenge in rodent models to malaria, where IgG2a antibodies were associated with protection in absence of detectable PvCSP-specific T cell responses...
April 18, 2017: Scientific Reports
Bridget E Barber, Giri S Rajahram, Matthew J Grigg, Timothy William, Nicholas M Anstey
BACKGROUND: The 2016 World Health Organization (WHO) World Malaria Report documents substantial progress towards control and elimination of malaria. However, major challenges remain. In some regions of Southeast Asia, the simian parasite Plasmodium knowlesi has emerged as an important cause of human malaria, and the authors believe this species warrants regular inclusion in the World Malaria Report. MAIN TEXT: Plasmodium knowlesi is the most common cause of malaria in Malaysia, and cases have also been reported in nearly all countries of Southeast Asia...
March 31, 2017: Malaria Journal
Caeul Lim, Selasi Dankwa, Aditya S Paul, Manoj T Duraisingh
Plasmodium falciparum and Plasmodium vivax account for most of the mortality and morbidity associated with malaria in humans. Research and control efforts have focused on infections caused by P. falciparum and P. vivax, but have neglected other malaria parasite species that infect humans. Additionally, many related malaria parasite species infect nonhuman primates (NHPs), and have the potential for transmission to humans. For malaria elimination, the varied and specific challenges of all of these Plasmodium species will need to be considered...
February 17, 2017: Cold Spring Harbor Perspectives in Medicine
Nicanor Obaldia, Michael G Stockelman, William Otero, Jennifer A Cockrill, Harini Ganeshan, Esteban N Abot, Jianfeng Zhang, Keith Limbach, Yupin Charoenvit, Denise L Doolan, De-Chu C Tang, Thomas L Richie
Malaria is caused by parasites of the genus Plasmodium, which are transmitted to humans by the bites of Anopheles mosquitoes. After the elimination of Plasmodium falciparum, it is predicted that Plasmodium vivax will remain an important cause of morbidity and mortality outside Africa, stressing the importance of developing a vaccine against P. vivax malaria. In this study, we assessed the immunogenicity and protective efficacy of two P. vivax antigens, apical membrane antigen 1 (AMA1) and the 42-kDa C-terminal fragment of merozoite surface protein 1 (MSP142) in a plasmid recombinant DNA prime/adenoviral (Ad) vector boost regimen in Aotus monkeys...
April 2017: Clinical and Vaccine Immunology: CVI
Eduardo Alves, Ahmed M Salman, Fabiana Leoratti, Cesar Lopez-Camacho, Martha Eva Viveros-Sandoval, Amar Lall, Aadil El-Turabi, Martin F Bachmann, Adrian V S Hill, Chris J Janse, Shahid M Khan, Arturo Reyes-Sandoval
Four different vaccine platforms, each targeting the human malaria parasite Plasmodium vivax cell-traversal protein for ookinetes and sporozoites (PvCelTOS), were generated and assessed for protective efficacy. These platforms consisted of a recombinant chimpanzee adenoviral vector 63 (ChAd63) expressing PvCelTOS (Ad), a recombinant modified vaccinia virus Ankara expressing PvCelTOS (MVA), PvCelTOS conjugated to bacteriophage Qβ virus-like particles (VLPs), and a recombinant PvCelTOS protein expressed in eukaryotic HEK293T cells (protein)...
April 2017: Clinical and Vaccine Immunology: CVI
Annie N Cowell, Dorothy E Loy, Sesh A Sundararaman, Hugo Valdivia, Kathleen Fisch, Andres G Lescano, G Christian Baldeviano, Salomon Durand, Vince Gerbasi, Colin J Sutherland, Debbie Nolder, Joseph M Vinetz, Beatrice H Hahn, Elizabeth A Winzeler
Whole-genome sequencing (WGS) of microbial pathogens from clinical samples is a highly sensitive tool used to gain a deeper understanding of the biology, epidemiology, and drug resistance mechanisms of many infections. However, WGS of organisms which exhibit low densities in their hosts is challenging due to high levels of host genomic DNA (gDNA), which leads to very low coverage of the microbial genome. WGS of Plasmodium vivax, the most widely distributed form of malaria, is especially difficult because of low parasite densities and the lack of an ex vivo culture system...
February 7, 2017: MBio
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
Elamaran Meibalan, Matthias Marti
Understanding transmission biology at an individual level is a key component of intervention strategies that target the spread of malaria parasites from human to mosquito. Gametocytes are specialized sexual stages of the malaria parasite life cycle developed during evolution to achieve crucial steps in transmission. As sexual differentiation and transmission are tightly linked, a deeper understanding of molecular and cellular events defining this relationship is essential to combat malaria. Recent advances in the field are gradually revealing mechanisms underlying sexual commitment, gametocyte sequestration, and dynamics of transmissible stages; however, key questions on fundamental gametocyte biology still remain...
March 1, 2017: Cold Spring Harbor Perspectives in Medicine
Angel Rosas-Aguirre, Dionicia Gamboa, Paulo Manrique, Jan E Conn, Marta Moreno, Andres G Lescano, Juan F Sanchez, Hugo Rodriguez, Hermann Silva, Alejandro Llanos-Cuentas, Joseph M Vinetz
Malaria in Peru, dominated by Plasmodium vivax, remains a public health problem. The 1990s saw newly epidemic malaria emerge, primarily in the Loreto Department in the Amazon region, including areas near to Iquitos, the capital city, but sporadic malaria transmission also occurred in the 1990s-2000s in both north-coastal Peru and the gold mining regions of southeastern Peru. Although a Global Fund-supported intervention (PAMAFRO, 2005-2010) was temporally associated with a decrease of malaria transmission, from 2012 to the present, both P...
December 28, 2016: American Journal of Tropical Medicine and Hygiene
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