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human malaria challenge

Anthony L Cunningham, Nathalie Garçon, Oberdan Leo, Leonard R Friedland, Richard Strugnell, Béatrice Laupèze, Mark Doherty, Peter Stern
In the 21st century, an array of microbiological and molecular allow antigens for new vaccines to be specifically identified, designed, produced and delivered with the aim of optimising the induction of a protective immune response against a well-defined immunogen. New knowledge about the functioning of the immune system and host pathogen interactions has stimulated the rational design of vaccines. The design toolbox includes vaccines made from whole pathogens, protein subunits, polysaccharides, pathogen-like particles, use of viral/bacterial vectors, plus adjuvants and conjugation technology to increase and broaden the immune response...
October 18, 2016: Vaccine
Olatunde Adesoro, Constance Shumba, John Kpamor, Jane Achan, Harriet Kivumbi, John Dada, Kolawole Maxwell, James Tibenderana, Madeline Marasciulo, Prudence Hamade, Olusola Oresanya, Joanita Nankabirwa, Ebenezer Baba
BACKGROUND: Innovative strategies are needed to reduce malaria mortality in high burden countries like Nigeria. Given that one of the important reasons for this high malaria mortality is delay in receiving effective treatment, improved access to such treatment is critical. Intramuscular artesunate could be used at lower-level facilities given its proven efficacy, ease of use and excellent safety profile. The objective of this study was therefore to explore health workers' perspectives on the possible use of intramuscular artesunate as definitive treatment for severe malaria at lower-level facilities, especially when access to referral facilities is challenging...
October 12, 2016: BMC Health Services Research
Arti Vashist, Ajeet Kaushik, Atul Vashist, Rahul Dev Jayant, Asahi Tomitaka, Sharif Ahmad, Y K Gupta, Madhavan Nair
Since centuries, the rapid spread and cure of infectious diseases have been a major concern to the progress and survival of humans. These diseases are a global burden and the prominent cause for worldwide deaths and disabilities. Nanomedicine has emerged as the most excellent tool to eradicate and halt their spread. Various nanoformulations (NFs) using advanced nanotechnology are in demand. Recently, hydrogel and nanogel based drug delivery devices have posed new prospects to simulate the natural intelligence of various biological systems...
October 18, 2016: Biomaterials Science
Claudia Surjadjaja, Asik Surya, J Kevin Baird
Endemic malaria occurs across much of the vast Indonesian archipelago. All five species of Plasmodium known to naturally infect humans occur here, along with 20 species of Anopheles mosquitoes confirmed as carriers of malaria. Two species of plasmodia cause the overwhelming majority and virtually equal shares of malaria infections in Indonesia: Plasmodium falciparum and Plasmodium vivax The challenge posed by P. vivax is especially steep in Indonesia because chloroquine-resistant strains predominate, along with Chesson-like strains that relapse quickly and multiple times at short intervals in almost all patients...
October 5, 2016: American Journal of Tropical Medicine and Hygiene
Yossef Alnasser, Cusi Ferradas, Taryn Clark, Maritza Calderon, Alejandro Gurbillon, Dionicia Gamboa, Uri S McKakpo, Isabella A Quakyi, Kwabena M Bosompem, David J Sullivan, Joseph M Vinetz, Robert H Gilman
Plasmodium vivax is the most prevalent cause of human malaria in the world and can lead to severe disease with high potential for relapse. Its genetic and geographic diversities make it challenging to control. P. vivax is understudied and to achieve control of malaria in endemic areas, a rapid, accurate, and simple diagnostic tool is necessary. In this pilot study, we found that a colorimetric system using AuNPs and MSP10 DNA detection in urine can provide fast, easy, and inexpensive identification of P. vivax...
October 2016: PLoS Neglected Tropical Diseases
Peter Dambach, Issouf Traoré, Achim Kaiser, Ali Sié, Rainer Sauerborn, Norbert Becker
BACKGROUND: Recent malaria control and elimination attempts show remarkable success in several parts of sub-Saharan Africa. Vector control via larval source management represents a new and to date underrepresented approach in low income countries to further reduce malaria transmission. Although the positive impact of such campaigns on malaria incidence has been researched, there is a lack of data on which prerequisites are needed for implementing such programs on a routine basis on large scale...
September 29, 2016: BMC Public Health
Cara Smith Gueye, Gretchen Newby, Jim Tulloch, Laurence Slutsker, Marcel Tanner, Roland D Gosling
BACKGROUND: A malaria eradication goal has been proposed, at the same time as a new global strategy and implementation framework. Countries are considering the strategies and tools that will enable progress towards malaria goals. The eliminating malaria case-study series reports were reviewed to identify successful programme management components using a cross-case study analytic approach. METHODS: Nine out of ten case-study reports were included in the analysis (Bhutan, Cape Verde, Malaysia, Mauritius, Namibia, Philippines, Sri Lanka, Turkey, Turkmenistan)...
2016: Malaria Journal
Damien R Drew, Danny W Wilson, Salenna R Elliott, Nadia Cross, Ulrich Terheggen, Anthony N Hodder, Peter M Siba, Kiprotich Chelimo, Arlene E Dent, James W Kazura, Ivo Mueller, James G Beeson
BACKGROUND: The polymorphic nature of many malaria vaccine candidates presents major challenges to achieving highly efficacious vaccines. Presently, there is very little knowledge on the prevalence and patterns of functional immune responses to polymorphic vaccine candidates in populations to guide vaccine design. A leading polymorphic vaccine candidate against blood-stage Plasmodium falciparum is apical membrane antigen 1 (AMA1), which is essential for erythrocyte invasion. The importance of AMA1 as a target of acquired human inhibitory antibodies, their allele specificity and prevalence in populations is unknown, but crucial for vaccine design...
September 23, 2016: BMC Medicine
Erika Jimena Dorado, Sheila Akinyi Okoth, Lidia Madeline Montenegro, Gustavo Diaz, John W Barnwell, Venkatachalam Udhayakumar, Claribel Murillo Solano
Most Plasmodium falciparum-detecting rapid diagnostic tests (RDTs) target histidine-rich protein 2 (PfHRP2). However, P. falciparum isolates with deletion of the pfhrp2 gene and its homolog gene, pfhrp3, have been detected. We carried out an extensive investigation on 365 P. falciparum dried blood samples collected from seven P. falciparum endemic sites in Colombia between 2003 and 2012 to genetically characterise and geographically map pfhrp2- and/or pfhrp3-negative P. falciparum parasites in the country. We found a high proportion of pfhrp2-negative parasites only in Amazonas (15/39; 38...
2016: PloS One
Nathalie Garçon, Alberta Di Pasquale
Adjuvants are substances added to vaccines to improve their immunogenicity. Used for more than 80 years, aluminum, the first adjuvant in human vaccines, proved insufficient to develop vaccines that could protect against new challenging pathogens such as HIV and malaria. New adjuvants and new combinations of adjuvants (Adjuvant Systems) have opened the door to the delivery of improved and new vaccines against re-emerging and difficult pathogens. Adjuvant Systems concept started through serendipity. The access to new developments in technology, microbiology and immunology have been instrumental for the dicephering of what they do and how they do it...
September 16, 2016: Human Vaccines & Immunotherapeutics
Robert A Mitchell, Rita Altszuler, Ute Frevert, Elizabeth H Nardin
Malaria eradication will require a combination of vector control, chemotherapy and an easily administered vaccine. Sterile immunity can be elicited in humans by immunization with sporozoites, the infective stage injected by bite of the mosquito vector, however, whole parasite vaccines present formidable logistical challenges for production, storage and administration. The "gold standard" for infectious disease eradiation, the Smallpox Eradication Programme, utilized mass immunization using the skin scarification (SS) route...
2016: Scientific Reports
Chester Joyner, Alberto Moreno, Esmeralda V S Meyer, Monica Cabrera-Mora, Jessica C Kissinger, John W Barnwell, Mary R Galinski
BACKGROUND: Plasmodium vivax infections in humans or in new world monkeys pose research challenges that necessitate the use of alternative model systems. Plasmodium cynomolgi is a closely related species that shares genetic and biological characteristics with P. vivax, including relapses. Here, the haematological dynamics and clinical presentation of sporozoite-initiated P. cynomolgi infections in Macaca mulatta (rhesus macaques) are evaluated over a 100-day period. METHODS: Five M...
2016: Malaria Journal
Mary F Fontana, Alyssa Baccarella, Joshua F Craft, Michelle J Boyle, Tara I McIntyre, Matthew D Wood, Kurt S Thorn, Chioma Anidi, Aqieda Bayat, Me Ree Chung, Rebecca Hamburger, Chris Y Kim, Emily Pearman, Jennifer Pham, Jia J Tang, Louis Boon, Moses R Kamya, Grant Dorsey, Margaret E Feeney, Charles C Kim
In humans, immunity to Plasmodium sp. generally takes the form of protection from symptomatic malaria (i.e., 'clinical immunity') rather than infection ('sterilizing immunity'). In contrast, mice infected with Plasmodium develop sterilizing immunity, hindering progress in understanding the mechanistic basis of clinical immunity. Here we present a novel model in which mice persistently infected with P. chabaudi exhibit limited clinical symptoms despite sustaining patent parasite burdens for many months. Characterization of immune responses in persistently infected mice revealed development of CD4+ T cell exhaustion, increased production of IL-10, and expansion of B cells with an atypical surface phenotype...
2016: PloS One
Jaishree Raman, Natashia Morris, John Frean, Basil Brooke, Lucille Blumberg, Philip Kruger, Aaron Mabusa, Eric Raswiswi, Bridget Shandukani, Eunice Misani, Mary-Anne Groepe, Devanand Moonasar
BACKGROUND: With a sustained national malaria incidence of fewer than one case per 1000 population at risk, in 2012 South Africa officially transitioned from controlling malaria to the ambitious goal of eliminating malaria within its borders by 2018. This review assesses the progress made in the 3 years since programme re-orientation while highlighting challenges and suggesting priorities for moving the malaria programme towards elimination. METHODS: National malaria case data and annual spray coverage data from 2010 until 2014 were assessed for trends...
2016: Malaria Journal
Francis B Ntumngia, Richard Thomson-Luque, Letícia de Menezes Torres, Karthigayan Gunalan, Luzia H Carvalho, John H Adams
UNLABELLED: Erythrocyte invasion by malaria parasites is essential for blood-stage development and an important determinant of host range. In Plasmodium vivax, the interaction between the Duffy binding protein (DBP) and its cognate receptor, the Duffy antigen receptor for chemokines (DARC), on human erythrocytes is central to blood-stage infection. Contrary to this established pathway of invasion, there is growing evidence of P. vivax infections occurring in Duffy blood group-negative individuals, suggesting that the parasite might have gained an alternative pathway to infect this group of individuals...
2016: MBio
Ross Boyce, Raquel Reyes, Michael Matte, Moses Ntaro, Edgar Mulogo, Joshua P Metlay, Lawrence Band, Mark J Siedner
BACKGROUND:  There are several mechanisms by which global climate change may impact malaria transmission. We sought to assess how the increased frequency of extreme precipitation events associated with global climate change will impact malaria transmission in highland areas of East Africa METHODS:  We used a differences-in-differences, quasi-experimental design to examine spatial variability in the incidence rate of laboratory-confirmed malaria cases and malaria-related hospitalizations comparing villages at (1) high vs...
August 17, 2016: Journal of Infectious Diseases
Xiangming Li, Jing Huang, Min Zhang, Ryota Funakoshi, Dutta Sheetij, Roberta Spaccapelo, Andrea Crisanti, Victor Nussenzweig, Ruth S Nussenzweig, Moriya Tsuji
A number of studies have shown that CD8+ T cells mediate protective anti-malaria immunity in a mouse model. However, whether human CD8+ T cells play a role in protection against malaria remains unknown. We recently established human immune system (HIS) mice harboring functional human CD8+ T cells (HIS-CD8 mice) by transduction with HLA-A∗0201 and certain human cytokines using recombinant adeno-associated virus-based gene transfer technologies. These HIS-CD8 mice mount a potent, antigen-specific HLA-A∗0201-restricted human CD8+ T-cell response upon immunization with a recombinant adenovirus expressing a human malaria antigen, the Plasmodium falciparum circumsporozoite protein (PfCSP), termed AdPfCSP...
August 31, 2016: Vaccine
Jona Walk, Remko Schats, Marijke C C Langenberg, Isaie J Reuling, Karina Teelen, Meta Roestenberg, Cornelus C Hermsen, Leo G Visser, Robert W Sauerwein
BACKGROUND: Controlled human malaria infection (CHMI) has become well-established in the evaluation of drugs and vaccines. Anti-malarial treatment is usually initiated when thick blood smears are positive by microscopy. This study explores the effects of using the more sensitive qPCR as the primary diagnostic test. METHODS: 1691 diagnostic blood samples were analysed by microscopy and qPCR from 115 volunteers (55 malaria naïve and 60 having received chemoprophylaxis and sporozoite immunization) who were challenged by five mosquitoes infected with Plasmodium falciparum sporozoites of the NF54 strain...
2016: Malaria Journal
Kathryn A Hjerrild, Jing Jin, Katherine E Wright, Rebecca E Brown, Jennifer M Marshall, Geneviève M Labbé, Sarah E Silk, Catherine J Cherry, Stine B Clemmensen, Thomas Jørgensen, Joseph J Illingworth, Daniel G W Alanine, Kathryn H Milne, Rebecca Ashfield, Willem A de Jongh, Alexander D Douglas, Matthew K Higgins, Simon J Draper
The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has recently emerged as a leading candidate antigen against the blood-stage human malaria parasite. However it has proved challenging to identify a heterologous expression platform that can produce a soluble protein-based vaccine in a manner compliant with current Good Manufacturing Practice (cGMP). Here we report the production of full-length PfRH5 protein using a cGMP-compliant platform called ExpreS(2), based on a Drosophila melanogaster Schneider 2 (S2) stable cell line system...
2016: Scientific Reports
Caeul Lim, Ligia Pereira, Kathryn Shaw Saliba, Anjali Mascarenhas, Jennifer N Maki, Laura Chery, Edwin Gomes, Pradipsinh K Rathod, Manoj T Duraisingh
Plasmodium vivax, the most widely distributed human malaria parasite, is restricted to reticulocytes, limiting its asexual proliferation. In recent years, cases of severe and high-level P. vivax parasitemia have been reported, challenging the assumption that all isolates are equally restricted. In this article, we analyze the reticulocyte preference of a large number of Indian P. vivax isolates. Our results show that P. vivax isolates significantly vary in their level of reticulocyte preference. In addition, by carefully staging the parasites, we find that P...
October 1, 2016: Journal of Infectious Diseases
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