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malaria transmission blocking

Kawsar R Talaat, Ruth D Ellis, Janet Hurd, Autumn Hentrich, Erin Gabriel, Noreen A Hynes, Kelly M Rausch, Daming Zhu, Olga Muratova, Raul Herrera, Charles Anderson, David Jones, Joan Aebig, Sarah Brockley, Nicholas J MacDonald, Xiaowei Wang, Michael P Fay, Sara A Healy, Anna P Durbin, David L Narum, Yimin Wu, Patrick E Duffy
Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from Pseudomonas aeruginosa. In this report, we describe results of an open-label, dose-escalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel®...
2016: PloS One
Neha Chaturvedi, Praveen K Bharti, Archana Tiwari, Neeru Singh
Transmission blocking malaria vaccines are aimed to block the development and maturity of sexual stages of parasite within mosquitoes. The vaccine candidate antigens (Pfs25, Pfs48/45, Pfs230) that have shown transmission blocking immunity in model systems are in different stages of development. These antigens are immunogenic with limited genetic diversity. Pfs25 is a leading candidate and currently in phase I clinical trial. Efforts are now focused on the cost-effective production of potent antigens using safe adjuvants and optimization of vaccine delivery system that are capable of inducing strong immune responses...
June 2016: Indian Journal of Medical Research
Amélie Le Bihan, Ruben de Kanter, Iñigo Angulo-Barturen, Christoph Binkert, Christoph Boss, Reto Brun, Ralf Brunner, Stephan Buchmann, Jeremy Burrows, Koen J Dechering, Michael Delves, Sonja Ewerling, Santiago Ferrer, Christoph Fischli, Francisco Javier Gamo-Benito, Nina F Gnädig, Bibia Heidmann, María Belén Jiménez-Díaz, Didier Leroy, Maria Santos Martínez, Solange Meyer, Joerg J Moehrle, Caroline L Ng, Rintis Noviyanti, Andrea Ruecker, Laura María Sanz, Robert W Sauerwein, Christian Scheurer, Sarah Schleiferboeck, Robert Sinden, Christopher Snyder, Judith Straimer, Grennady Wirjanata, Jutta Marfurt, Ric N Price, Thomas Weller, Walter Fischli, David A Fidock, Martine Clozel, Sergio Wittlin
BACKGROUND: Artemisinin resistance observed in Southeast Asia threatens the continued use of artemisinin-based combination therapy in endemic countries. Additionally, the diversity of chemical mode of action in the global portfolio of marketed antimalarials is extremely limited. Addressing the urgent need for the development of new antimalarials, a chemical class of potent antimalarial compounds with a novel mode of action was recently identified. Herein, the preclinical characterization of one of these compounds, ACT-451840, conducted in partnership with academic and industrial groups is presented...
October 2016: PLoS Medicine
Christopher Dean Goodman, Ingvild Austarheim, Vanessa Mollard, Bertin Mikolo, Karl Egil Malterud, Geoffrey I McFadden, Helle Wangensteen
BACKGROUND: Zanthoxylum heitzii (Rutaceae) (olon) is used in traditional medicine in Central and West Africa to treat malaria. To identify novel compounds with anti-parasitic activity and validate medicinal usage, extracts and compounds isolated from this tree were tested against the erythrocytic stages of the human malaria parasite Plasmodium falciparum and for inhibition of transmission in rodent malaria parasite Plasmodium berghei. RESULTS: Hexane bark extract showed activity against P...
2016: Malaria Journal
Robert J Hart, Emmanuel Cornillot, Amanah Abraham, Emily Molina, Catherine S Nation, Choukri Ben Mamoun, Ahmed S I Aly
The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B5) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes (PanK1 and PanK2) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown...
2016: Scientific Reports
Sofia Tapanelli, Giuseppina Chianese, Leonardo Lucantoni, Rakiswendé Serge Yerbanga, Annette Habluetzel, Orazio Taglialatela-Scafati
Azadirachta indica, known as neem tree and traditionally called "nature's drug store" makes part of several African pharmacopeias and is widely used for the preparation of homemade remedies and commercial preparations against various illnesses, including malaria. Employing a bio-guided fractionation approach, molecules obtained from A. indica ripe and green fruit kernels were tested for activity against early sporogonic stages of Plasmodium berghei, the parasite stages that develop in the mosquito mid gut after an infective blood meal...
October 2016: Fitoterapia
Kazutoyo Miura, Will J R Stone, Karin M Koolen, Bingbing Deng, Luwen Zhou, Geert-Jan van Gemert, Emily Locke, Merribeth Morin, Teun Bousema, Robert W Sauerwein, Carole A Long, Koen J Dechering
BACKGROUND: An effective malaria transmission-blocking vaccine may play an important role in malaria elimination efforts, and a robust biological assay is essential for its development. The standard membrane-feeding assay (SMFA) for Plasmodium falciparum infection of mosquitoes is considered a "gold standard" assay to measure transmission-blocking activity of test antibodies, and has been utilized widely in both non-clinical and clinical studies. While several studies have discussed the inherent variability of SMFA within a study group, there has been no assessment of inter-laboratory variation...
2016: Malaria Journal
Daisuke S Yamamoto, Megumi Sumitani, Katsumi Kasashima, Hideki Sezutsu, Hiroyuki Matsuoka
Malaria is an important global public health challenge, and is transmitted by anopheline mosquitoes during blood feeding. Mosquito vector control is one of the most effective methods to control malaria, and population replacement with genetically engineered mosquitoes to block its transmission is expected to become a new vector control strategy. The salivary glands are an effective target tissue for the expression of molecules that kill or inactivate malaria parasites. Moreover, salivary gland cells express a large number of molecules that facilitate blood feeding and parasite transmission to hosts...
September 2016: PLoS Pathogens
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
Maurice M Sandeu, Luc Abate, Majoline T Tchioffo, Albert N Bayibéki, Parfait H Awono-Ambéné, Sandrine E Nsango, Cédric B Chesnais, Rhoel R Dinglasan, Thierry de Meeûs, Isabelle Morlais
Progress in malaria control has led to a significant reduction of the malaria burden. Interventions that interrupt transmission are now needed to achieve the elimination goal. Transmission-blocking vaccines (TBV) that aim to prevent mosquito infections represent promising tools and several vaccine candidates targeting different stages of the parasite's lifecycle are currently under development. A mosquito-midgut antigen, the anopheline alanyl aminopeptidase (AnAPN1) is one of the lead TBV candidates; antibodies against AnAPN1 prevent ookinete invasion...
August 23, 2016: Infection, Genetics and Evolution
Michael J Delves, Ursula Straschil, Andrea Ruecker, Celia Miguel-Blanco, Sara Marques, Jake Baum, Robert E Sinden
The prevention of parasite transmission from the human host to the mosquito has been recognized as a vital tool for malaria eradication campaigns. However, transmission-blocking antimalarial drug and/or vaccine discovery and development is currently hampered by the expense and difficulty of producing mature Plasmodium falciparum gametocytes in vitro-the parasite stage responsible for mosquito infection. Current protocols for P. falciparum gametocyte culture usually require complex parasite synchronization and addition of stimulating and/or inhibitory factors, and they may not have demonstrated the essential property of mosquito infectivity...
September 2016: Nature Protocols
Guofa Zhou, Virginia Wiseman, Harrysone E Atieli, Ming-Chieh Lee, Andrew K Githeko, Guiyun Yan
BACKGROUND: The massive scale-up of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) has led to a substantial increase in malaria vector insecticide resistance as well as in increased outdoor transmission, both of which hamper the effectiveness and efficiency of ITN and IRS. Long-lasting microbial larvicide can be a cost-effective new supplemental intervention tool for malaria control. METHODS/DESIGN: We will implement the long-lasting microbial larvicide intervention in 28 clusters in two counties in western Kenya...
2016: Trials
Sung-Jae Cha, Min-Sik Kim, Akhilesh Pandey, Marcelo Jacobs-Lorena
Malaria transmission begins when an infected mosquito delivers Plasmodium sporozoites into the skin. The sporozoite subsequently enters the circulation and infects the liver by preferentially traversing Kupffer cells, a macrophage-like component of the liver sinusoidal lining. By screening a phage display library, we previously identified a peptide designated P39 that binds to CD68 on the surface of Kupffer cells and blocks sporozoite traversal. In this study, we show that the P39 peptide is a structural mimic of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) on the sporozoite surface and that GAPDH directly interacts with CD68 on the Kupffer cell surface...
September 19, 2016: Journal of Experimental Medicine
Nathan J Dennison, Raúl G Saraiva, Chris M Cirimotich, Godfree Mlambo, Emmanuel F Mongodin, George Dimopoulos
BACKGROUND: Malaria exerts a tremendous socioeconomic impact worldwide despite current control efforts, and novel disease transmission-blocking strategies are urgently needed. The Enterobacter bacterium Esp_Z, which is naturally harboured in the mosquito midgut, can inhibit the development of Plasmodium parasites prior to their invasion of the midgut epithelium through a mechanism that involves oxidative stress. Here, a multifaceted approach is used to study the tripartite interactions between the mosquito, Esp_Z and Plasmodium, towards addressing the feasibility of using sugar-baited exposure of mosquitoes to the Esp_Z bacterium for interruption of malaria transmission...
2016: Malaria Journal
Shwu-Maan Lee, Chia-Kuei Wu, Jordan Plieskatt, David H McAdams, Kazutoyo Miura, Chris Ockenhouse, C Richter King
BACKGROUND: Transmission-blocking vaccines (TBVs) have become a focus of strategies to control and eventually eliminate malaria as they target the entry of sexual stage into the Anopheles stephensi mosquito thereby preventing transmission, an essential component of the parasite life cycle. Such vaccines are envisioned as complements to vaccines that target human infection, such as RTS,S as well as drug treatment, and vector control strategies. A number of conserved proteins, including Pfs25, have been identified as promising TBV targets in research or early stage development...
2016: Malaria Journal
David Bell, Alessandra E Fleurent, Michael C Hegg, John D Boomgard, Caitlin C McConnico
Despite advances in diagnostic technology, significant gaps remain in access to malaria diagnosis. Accurate diagnosis and misdiagnosis leads to unnecessary waste of resources, poor disease management, and contributes to a cycle of poverty in low-resourced communities. Despite much effort and investment, few new technologies have reached the field in the last 30 years aside from lateral flow assays. This suggests that much diagnostic development effort has been misdirected, and/or that there are fundamental blocks to introduction of new technologies...
2016: Malaria Journal
Li Zheng, Wei Pang, Zanmei Qi, Enjie Luo, Liwang Cui, Yaming Cao
BACKGROUND: Transmission-blocking vaccine (TBV) is a promising strategy for interrupting the malaria transmission cycle. Current TBV candidates include both pre- and post-fertilization antigens expressed during sexual development of the malaria parasites. METHODS: We tested whether a TBV design combining two sexual-stage antigens has better transmission-blocking activity. Using the rodent malaria model Plasmodium yoelii, we pursued a DNA vaccination strategy with genes encoding the gametocyte antigen Pys48/45 and the major ookinete surface protein Pys25...
2016: Parasites & Vectors
Noah H Paul, Arthur Vengesai, Takafira Mduluza, James Chipeta, Nicholas Midzi, Geetha P Bansal, Nirbhay Kumar
Malaria continues to cause alarming morbidity and mortality in more than 100 countries worldwide. Antigens in the various life cycle stages of malaria parasites are presented to the immune system during natural infection and it is widely recognized that after repeated malaria exposure, adults develop partially protective immunity. Specific antigens of natural immunity represent among the most important targets for the development of malaria vaccines. Immunity against the transmission stages of the malaria parasite represents an important approach to reduce malaria transmission and is believed to become an important tool for gradual elimination of malaria...
November 2016: Acta Tropica
Kristina S Wickham, Paul C Baresel, Sean R Marcsisin, Jason Sousa, Chau T Vuong, Gregory A Reichard, Brice Campo, Babu L Tekwani, Larry A Walker, Rosemary Rochford
Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) are at risk for developing hemolytic anemia when given the antimalarial drug primaquine (PQ). The WHO Evidence Review Group released a report suggesting that mass administration of a single dose of PQ at 0.25 mg of base/kg of body weight (mpk) (mouse equivalent of 3.125 mpk) could potentially reduce malaria transmission based on its gametocytocidal activity and could be safely administered to G6PD-deficient individuals, but there are limited safety data available confirming the optimum single dose of PQ...
October 2016: Antimicrobial Agents and Chemotherapy
Rajiv Kumar Gupta, Sunil Kumar Raina, Tajali N Shora, Rayaz Jan, Renu Sharma, Shahid Hussain
INTRODUCTION: An extensive search on PubMed reveals very little in terms of evidence regarding the current knowledge, attitude, and practices (KAP) of the population in general and rural population, in particular, in this part of the country. Therefore, a study was conducted with the aim to assess the communities' knowledge of malaria transmission, recognition of signs and symptoms, treatment seeking. MATERIALS AND METHODS: A stratified two-stage design was used to conduct a house-to-house survey using a semi-structured questionnaire in RS Pura block of Jammu District of Jammu and Kashmir State in North India...
January 2016: Journal of Family Medicine and Primary Care
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