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malaria transmission blocking

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https://www.readbyqxmd.com/read/29219249/activities-of-11-azaartemisinin-and-n-sulfonyl-derivatives-against-asexual-and-transmissible-malaria-parasites
#1
Rozanne Harmse, Dina Coertzen, Ho Ning Wong, Frans J Smit, Mariette E van der Watt, Janette Reader, Sindiswe H Nondaba, Lyn-Marie Birkholtz, Richard K Haynes, David D N'Da
Dihydroartemisinin (DHA), either used in its own right or as the active drug generated in vivo from the other artemisinins in current clinical use-artemether and artesunate-induces quiescence in ring-stage parasites of Plasmodium falciparum (Pf). This induction of quiescence is linked to artemisinin resistance. Thus, we have turned to structurally disparate artemisinins that are incapable of providing DHA on metabolism. Accordingly, 11-azaartemisinin 5 and selected N-sulfonyl derivatives were screened against intraerythrocytic asexual stages of drug-sensitive Pf NF54 and drug-resistant K1 and W2 parasites...
December 8, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29190291/malera-an-updated-research-agenda-for-diagnostics-drugs-vaccines-and-vector-control-in-malaria-elimination-and-eradication
#2
(no author information available yet)
Since the turn of the century, a remarkable expansion has been achieved in the range and effectiveness of products and strategies available to prevent, treat, and control malaria, including advances in diagnostics, drugs, vaccines, and vector control. These advances have once again put malaria elimination on the agenda. However, it is clear that even with the means available today, malaria control and elimination pose a formidable challenge in many settings. Thus, currently available resources must be used more effectively, and new products and approaches likely to achieve these goals must be developed...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29162427/disulfide-bond-mapping-of-pfs25-a-recombinant-malaria-transmission-blocking-vaccine-candidate
#3
Shwu-Maan Lee, Jordan Plieskatt, C Richter King
A liquid chromatography tandem-mass spectrometry method was developed to map the eleven disulfide bonds in Pfs25, a malaria transmission-blocking vaccine candidate. The compact and complex nature of Pfs25 has led to difficulties in prior peptide mapping efforts. Here, we report confirmation of proper disulfide pairing of a recombinant Pfs25, by optimizing denaturation and digestion with trypsin/Lys-C. The digested peptides were separated by reversed phase HPLC to obtain the peptide map and elucidate the disulfide linkages...
November 18, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/29161848/complex-wolbachia-infection-dynamics-in-mosquitoes-with-imperfect-maternal-transmission
#4
Bo Zheng, Wenliang Guo, Linchao Hu, Mugen Huang, Jianshe Yu
Dengue, malaria, and Zika are dangerous diseases primarily transmitted by Aedes aegypti, Aedes albopictus, and Anopheles stephensi. In the last few years, a new disease control method, besides pesticide spraying to kill mosquitoes, has been developed by releasing mosquitoes carrying bacterium Wolbachia into the natural areas to infect the wild population of mosquitoes and block disease transmission. The bacterium is transmitted by infected mothers and the maternal transmission was assumed to be perfect in virtually all previous models...
April 1, 2018: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/29155091/dynamic-molecular-events-associated-to-plasmodium-berghei-gametogenesis-through-proteomic-approach
#5
Carlos H S Garcia, Delphine Depoix, Rayner M L Queiroz, Jaques M F Souza, Wagner Fontes, Marcelo V de Sousa, Marlon D M Santos, Paulo C Carvalho, Philippe Grellier, Sébastien Charneau
Plasmodium mature sexual cycle occurs in the vector mosquitoes and ensures the transmission to a new host. Gametogenesis takes place within minutes in the vector midgut. Gametocytes have to complete a deep nuclear reorganization, quick differentiation, and in the case of male gametocytes, intracytoplasmic flagellum assembly that results in free-swimming microgametes required for macrogamete fertilization. In efforts to improve our knowledge of molecular mechanisms involved in gamete morphogenesis, we carried out a nanoLC/MSMS based quantitative proteomic analysis throughout the xanthurenic acid-induced gametogenesis of the rodent parasite P...
November 15, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29153778/the-frontline-of-controlled-human-malaria-infections-a-report-from-the-controlled-human-infection-models-workshop-in-leiden-university-medical-centre-5-may-2016
#6
Meta Roestenberg, Benjamin Mordmüller, Chris Ockenhouse, Annie Mo, Maria Yazdanbakhsh, Peter G Kremsner
Controlled Human Malaria Infection (CHMI) is the most practiced controlled human infection model nowadays and there is an exponential increase in implementation of the model worldwide. During the Controlled Human Infection Models Workshop in Leiden, one day was dedicated to the discussion of the advances made and gaps in Controlled Human Malaria Infection (CHMI) trials. Factors contributing to this impressive expansion in the number of CHMI trials have been related to the ability to perform CHMI using injectable cryopreserved sporozoites (a product from Sanaria Inc...
November 16, 2017: Vaccine
https://www.readbyqxmd.com/read/29152597/identification-of-spiroplasmainsolitum-symbionts-in-anopheles-gambiae
#7
Sharon T Chepkemoi, Enock Mararo, Hellen Butungi, Juan Paredes, Daniel Masiga, Steven P Sinkins, Jeremy K Herren
Background: Insect symbionts have the potential to block the transmission of vector-borne diseases by their hosts. The advancement of a symbiont-based transmission blocking strategy for malaria requires the identification and study of Anopheles symbionts. Methods: High throughput 16S amplicon sequencing was used to profile the bacteria associated with Anopheles gambiae sensu lato and identify potential symbionts. The polymerase chain reaction (PCR) with specific primers were subsequently used to monitor symbiont prevalence in field populations, as well as symbiont transmission patterns...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/29146922/molecular-definition-of-multiple-sites-of-antibody-inhibition-of-malaria-transmission-blocking-vaccine-antigen-pfs25
#8
Stephen W Scally, Brandon McLeod, Alexandre Bosch, Kazutoyo Miura, Qi Liang, Sean Carroll, Sini Reponen, Ngan Nguyen, Eldar Giladi, Sebastian Rämisch, Vidadi Yusibov, Allan Bradley, Franck Lemiale, William R Schief, Daniel Emerling, Paul Kellam, C Richter King, Jean-Philippe Julien
The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29132995/comparative-functional-potency-of-dna-vaccines-encoding-plasmodium-falciparum-transmission-blocking-target-antigens-pfs48-45-and-pfs25-administered-alone-or-in-combination-by-in-vivo-electroporation-in-rhesus-macaques
#9
Dibyadyuti Datta, Geetha P Bansal, Brooke Grasperge, Dale S Martin, Mario Philipp, Dietlind Gerloff, Barry Ellefsen, Drew Hannaman, Nirbhay Kumar
Antibodies recognizing conformational epitopes in Pfs48/45, an antigen expressed on the surface of Plasmodium falciparum gametes and zygotes, have firmly established Pfs48/45 as a promising transmission blocking vaccine (TBV) candidate. However, it has been difficult to reproducibly express Pfs48/45 in a variety of recombinant expression systems. The goal of our studies was to evaluate functional immunogenicity of Pfs48/45 using DNA vaccine format in rhesus macaques. An additional goal was to ensure that when used in combination with another malarial antigen, specific immunity to both antigens was not compromised...
November 10, 2017: Vaccine
https://www.readbyqxmd.com/read/29132428/characterization-of-pb51-in-plasmodium-berghei-as-a-malaria-vaccine-candidate-targeting-both-asexual-erythrocytic-proliferation-and-transmission
#10
Jian Wang, Wenqi Zheng, Fei Liu, Yaru Wang, Yiwen He, Li Zheng, Qi Fan, Enjie Luo, Yaming Cao, Liwang Cui
BACKGROUND: A vaccine that targets multiple developmental stages of malaria parasites would be an effective tool for malaria control and elimination. METHODS: A conserved gene in Plasmodium, the Plasmodium berghei gene (PBANKA_020570) encoding a 51 kDa protein (pb51 gene), was identified through search of the PlasmoDB database using a combination of expression and protein localization criteria. A partial domain of the Pb51 protein was expressed in a prokaryotic expression system (rPb51) and used for immunization in mice...
November 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29129376/lysophosphatidylcholine-regulates-sexual-stage-differentiation-in-the-human-malaria-parasite-plasmodium-falciparum
#11
Nicolas M B Brancucci, Joseph P Gerdt, ChengQi Wang, Mariana De Niz, Nisha Philip, Swamy R Adapa, Min Zhang, Eva Hitz, Igor Niederwieser, Sylwia D Boltryk, Marie-Claude Laffitte, Martha A Clark, Christof Grüring, Deepali Ravel, Alexandra Blancke Soares, Allison Demas, Selina Bopp, Belén Rubio-Ruiz, Ana Conejo-Garcia, Dyann F Wirth, Edyta Gendaszewska-Darmach, Manoj T Duraisingh, John H Adams, Till S Voss, Andrew P Waters, Rays H Y Jiang, Jon Clardy, Matthias Marti
Transmission represents a population bottleneck in the Plasmodium life cycle and a key intervention target of ongoing efforts to eradicate malaria. Sexual differentiation is essential for this process, as only sexual parasites, called gametocytes, are infective to the mosquito vector. Gametocyte production rates vary depending on environmental conditions, but external stimuli remain obscure. Here, we show that the host-derived lipid lysophosphatidylcholine (LysoPC) controls P. falciparum cell fate by repressing parasite sexual differentiation...
November 2, 2017: Cell
https://www.readbyqxmd.com/read/29128668/inhibition-of-the-complement-system-by-saliva-of-anopheles-nyssorhynchus-aquasalis
#12
Antonio Ferreira Mendes-Sousa, Vladimir Fazito Vale, Daniel Costa Queiroz, Adalberto Alves Pereira-Filho, Naylene Carvalho Sales da Silva, Leonardo Barbosa Koerich, Luciano Andrade Moreira, Marcos Horácio Pereira, Maurício Roberto Sant'Anna, Ricardo Nascimento Araújo, John Andersen, Jesus Gilberto Valenzuela, Nelder Figueiredo Gontijo
Anopheline mosquitoes are vectors of malaria parasites. Their saliva contains anti-hemostatic and immune-modulator molecules that favor blood feeding and parasite transmission. In this study, we describe the inhibition of the alternative pathway of the complement system (AP) by Anopheles aquasalis salivary gland extracts (SGE). According to our results, the inhibitor present in SGE acts on the initial step of the AP blocking deposition of C3b on the activation surfaces. Properdin, which is a positive regulatory molecule of the AP, binds to SGE...
November 8, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29092797/gold-nanoparticles-against-parasites-and-insect-vectors
#13
REVIEW
Giovanni Benelli
Nanomaterials are currently considered for many biological, biomedical and environmental purposes, due to their outstanding physical and chemical properties. The synthesis of gold nanoparticles (Au NPs) is of high interest for research in parasitology and entomology, since these nanomaterials showed promising applications, ranging from detection techniques to drug development, against a rather wide range of parasites of public health relevance, as well as on insect vectors. Here, I reviewed current knowledge about the bioactivity of Au NPs on selected insect species of public health relevance, including major mosquito vectors, such as Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus...
October 29, 2017: Acta Tropica
https://www.readbyqxmd.com/read/29089373/functional-characterization-and-comparison-of-plasmodium-falciparum-proteins-as-targets-of-transmission-blocking-antibodies
#14
Daria Nikolaeva, Joseph J Illingworth, Kazutoyo Miura, Daniel Gw Alanine, Iona J Brian, Yuanyuan Li, Alex J Fyfe, Dari F Da, Anna Cohuet, Carole A Long, Simon J Draper, Sumi Biswas
Plasmodium falciparum malaria continues to evade control efforts, utilizing highly specialized sexual-stages to transmit infection between the human host and mosquito vector. In a vaccination model, antibodies directed to sexual-stage antigens, when ingested in the mosquito blood meal, can inhibit parasite growth in the midgut and consequently arrest transmission. Despite multiple datasets for the Plasmodium sexual-stage transcriptome and proteome, there have been no rational screens to identify candidate antigens for transmission-blocking vaccine (TBV) development...
October 31, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29079720/a-global-survey-of-atpase-activity-in-plasmodium-falciparum-asexual-blood-stages-and-gametocytes
#15
Corrie Ortega, Andrew Frando, Bobbie-Jo Webb-Robertson, Lindsey N Anderson, Neil D Fleck, Erika L Flannery, Matthew Fishbaugher, Taylor A Murphree, Joshua R Hansen, Richard D Smith, Stefan Hi Kappe, Aaron Wright, Christoph Grundner
Effective malaria control and elimination in hyperendemic areas of the world will require treatment of the Plasmodium falciparum (Pf) blood stage that causes disease as well as the gametocyte stage that is required for transmission from humans to the mosquito vector. Most currently used therapies do not kill gametocytes, a highly specialized, non-replicating sexual parasite stage. Further confounding next generation drug development against Pf is the unknown metabolic state of the gametocyte and the lack of known biochemical activity for most parasite gene products in general...
October 27, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29042501/plasmodium-falciparum-calcium-dependent-protein-kinase-2-is-critical-for-male-gametocyte-exflagellation-but-not-essential-for-asexual-proliferation
#16
Abhisheka Bansal, Alvaro Molina-Cruz, Joseph Brzostowski, Jianbing Mu, Louis H Miller
Drug development efforts have focused mostly on the asexual blood stages of the malaria parasite Plasmodium falciparum Except for primaquine, which has its own limitations, there are no available drugs that target the transmission of the parasite to mosquitoes. Therefore, there is a need to validate new parasite proteins that can be targeted for blocking transmission. P. falciparum calcium-dependent protein kinases (PfCDPKs) play critical roles at various stages of the parasite life cycle and, importantly, are absent in the human host...
October 17, 2017: MBio
https://www.readbyqxmd.com/read/29041962/comparative-assessment-of-an-gambiae-and-an-stephensi-mosquitoes-to-determine-transmission-reducing-activity-of-antibodies-against-p-falciparum-sexual-stage-antigens
#17
Maarten Eldering, Anaïs Bompard, Kazutoyo Miura, Will Stone, Isabelle Morlais, Anna Cohuet, Geert-Jan van Gemert, Patrick M Brock, Sanna R Rijpma, Marga van de Vegte-Bolmer, Wouter Graumans, Rianne Siebelink-Stoter, Dari F Da, Carole A Long, Merribeth J Morin, Robert W Sauerwein, Thomas S Churcher, Teun Bousema
BACKGROUND: With the increasing interest in vaccines to interrupt malaria transmission, there is a demand for harmonization of current methods to assess Plasmodium transmission in laboratory settings. Potential vaccine candidates are currently tested in the standard membrane feeding assay (SMFA) that commonly relies on Anopheles stephensi mosquitoes. Other mosquito species including Anopheles gambiae are the dominant malaria vectors for Plasmodium falciparum in sub-Saharan Africa. METHODS: Using human serum and monoclonal pre-fertilization (anti-Pfs48/45) and post-fertilization (anti-Pfs25) antibodies known to effectively inhibit sporogony, we directly compared SMFA based estimates of transmission-reducing activity (TRA) for An...
October 17, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29029367/genetic-diversity-of-plasmodium-falciparum-merozoite-surface-protein-1-block-2-glutamate-rich-protein-and-sexual-stage-antigen-pfs25-from-chandigarh-north-india
#18
Hargobinder Kaur, Rakesh Sehgal, Kapil Goyal, Nikita Makkar, Richa Yadav, Praveen K Bharti, Neeru Singh, Nilanju P Sarmah, Pradymna K Mohapatra, Jagadish Mahanta, Devendra Bansal, Ali A Sultan, Jagat R Kanwar
OBJECTIVE: To elucidate the genetic diversity of P. falciparum in residual transmission foci of northern India. METHODS: Clinically suspected malaria patients were screened for malaria infection by microscopy. 48 P. falciparum-infected patients were enrolled from two tertiary care hospitals in Chandigarh, India. Blood samples were collected from enrolled patients, genomic DNA extraction and nested PCR was performed for further species confirmation. Sanger sequencing was carried out using block 2 region of msp1, R2 region of glurp and pfs25 specific primers...
October 13, 2017: Tropical Medicine & International Health: TM & IH
https://www.readbyqxmd.com/read/28993460/evaluation-of-a-plasmodium-specific-carrier-protein-to-enhance-production-of-recombinant-pfs25-a-leading-transmission-blocking-vaccine-candidate
#19
Elizabeth M Parzych, Kazutoyo Miura, Aarti Ramanathan, Carole A Long, James M Burns
Challenges with the production and suboptimal immunogenicity of malaria vaccine candidates have slowed the development of a Plasmodium falciparum multi-antigen vaccine. Attempting to resolve these issues, we focused on the use of the highly immunogenic merozoite surface protein 8 (MSP8) as a vaccine carrier protein. Previously, we showed that genetic fusion of the C-terminal 19 kDa fragment of merozoite surface protein 1 (MSP119) to PfMSP8 facilitated antigen production, folding and induction of neutralizing antibodies to conformational B cell epitopes of MSP119 Here, using the PfMSP1/8 construct, we further optimized the rPfMSP8 carrier by introduction of two cysteine to serine substitutions (CΔS) to improve the yield of monomeric product...
October 9, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28985225/disrupting-assembly-of-the-inner-membrane-complex-blocks-plasmodium-falciparum-sexual-stage-development
#20
Molly Parkyn Schneider, Boyin Liu, Philipp Glock, Annika Suttie, Emma McHugh, Dean Andrew, Steven Batinovic, Nicholas Williamson, Eric Hanssen, Paul McMillan, Marion Hliscs, Leann Tilley, Matthew W A Dixon
Transmission of malaria parasites relies on the formation of a specialized blood form called the gametocyte. Gametocytes of the human pathogen, Plasmodium falciparum, adopt a crescent shape. Their dramatic morphogenesis is driven by the assembly of a network of microtubules and an underpinning inner membrane complex (IMC). Using super-resolution optical and electron microscopies we define the ultrastructure of the IMC at different stages of gametocyte development. We characterize two new proteins of the gametocyte IMC, called PhIL1 and PIP1...
October 2017: PLoS Pathogens
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