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human malaria challenge

Meta Roestenberg, Marie-Astrid Hoogerwerf, Daniela M Ferreira, Benjamin Mordmüller, Maria Yazdanbakhsh
Controlled human infection (CHI) trials, in which healthy volunteers are experimentally infected, can accelerate the development of novel drugs and vaccines for infectious diseases of global importance. The use of CHI models is expanding from around 60 studies in the 1970s to more than 120 publications in this decade, primarily for influenza, rhinovirus, and malaria. CHI trials have provided landmark data for several registered drugs and vaccines, and have generated unprecedented scientific insights. Because of their invasive nature, CHI studies demand critical ethical review according to established frameworks...
June 8, 2018: Lancet Infectious Diseases
Itziar Ubillos, Alfons Jiménez, Marta Vidal, Paul W Bowyer, Deepak Gaur, Sheetij Dutta, Benoit Gamain, Ross Coppel, Virander Chauhan, David Lanar, Chetan Chitnis, Evelina Angov, James Beeson, David Cavanagh, Joseph J Campo, Ruth Aguilar, Carlota Dobaño
BACKGROUND: The quantitative suspension array technology (qSAT) is a useful platform for malaria immune marker discovery. However, a major challenge for large sero-epidemiological and malaria vaccine studies is the comparability across laboratories, which requires the access to standardized control reagents for assay optimization, to monitor performance and improve reproducibility. Here, the Plasmodium falciparum antibody reactivities of the newly available WHO reference reagent for anti-malaria human plasma (10/198) and of additional customized positive controls were examined with seven in-house qSAT multiplex assays measuring IgG, IgG1-4 subclasses, IgM and IgE against a panel of 40 antigens...
June 1, 2018: Malaria Journal
Maureen Njue, Patricia Njuguna, Melissa C Kapulu, Gladys Sanga, Philip Bejon, Vicki Marsh, Sassy Molyneux, Dorcas Kamuya
Background: The range and amount of volunteer infection studies, known as Controlled Human Infection Model (CHMI) studies, in Low-Middle Income Countries (LMICs) is increasing with rapid technological advancement, world-class laboratory facilities and increasing capacity development initiatives. However, the ethical issues these studies present in LMICs have not been empirically studied. We present findings of a descriptive social science study nested within a malaria volunteer infection study, on-going at the time of writing, at the KEMRI-Wellcome Trust Research Programme (KWTRP) on the Kenyan Coast...
2018: Wellcome Open Research
Catherine Yuk-Ping Lo
BACKGROUND: China has experienced unprecedented economic growth since the 1980s. Despite this impressive economic development, this growth exists side by side with the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and severe acute respiratory syndrome (SARS) crises and the persisting deficiencies in public health provision in China. Acknowledging the prevailing health problems, the Chinese government has encouraged the development of health non-governmental organizations (NGOs) to respond to the health challenges and address the gaps in public health provision of the government...
May 16, 2018: Globalization and Health
Nisha Singh, Zeeshan Ahmad, Navin Baid, Ashwani Kumar
Infectious diseases are a major challenge in management of human health worldwide. Recent literature suggests that host immune system could be modulated to ameliorate the pathogenesis of infectious disease. Heme oxygenase (HMOX1) is a key regulator of cellular signaling and it could be modulated using pharmacological reagents. HMOX1 is a cytoprotective enzyme that degrades heme to generate carbon monoxide (CO), biliverdin, and molecular iron. CO and biliverdin (or bilirubin derived from it) can restrict the growth of a few pathogens...
May 14, 2018: IUBMB Life
Mahdi Amiri, Abbasali Nourian, Maryam Khoshkam, Ali Ramazani
Due to the challenges in the control, prevention, and eradication of parasitic diseases like malaria, there is an urgent need to discover new therapeutic agents. Plant-derived medicines may open new ways in the field of antiplasmodial therapy. This study is aimed to investigate the toxicity and in vivo antiplasmodial activity of apigenin, a dietary flavonoid. Apigenin cytotoxicity was investigated on Huh7 cell line, brine shrimp (Artemia salina) larva, and human red blood cells. In vivo toxicity of apigenin was assessed by metabolomics approaches...
May 11, 2018: Phytotherapy Research: PTR
Keillen M Martins-Campos, Andrea Kuehn, Anne Almeida, Ana Paula M Duarte, Vanderson S Sampaio, Íria C Rodriguez, Sara G M da Silva, Claudia María Ríos-Velásquez, José Bento Pereira Lima, Paulo Filemon Paolucci Pimenta, Quique Bassat, Ivo Müller, Marcus Lacerda, Wuelton M Monteiro, Maria das Graças V Barbosa Guerra
BACKGROUND: Asymptomatic individuals are one of the major challenges for malaria elimination programs in endemic areas. In the absence of clinical symptoms and with a lower parasite density they constitute silent reservoirs considered important for maintaining transmission of human malaria. Studies from Brazil have shown that infected individuals may carry these parasites for long periods. RESULTS: Patients were selected from three periurban endemic areas of the city of Manaus, in the western Brazilian Amazon...
May 4, 2018: Parasites & Vectors
Min Zhang, Chengqi Wang, Thomas D Otto, Jenna Oberstaller, Xiangyun Liao, Swamy R Adapa, Kenneth Udenze, Iraad F Bronner, Deborah Casandra, Matthew Mayho, Jacqueline Brown, Suzanne Li, Justin Swanson, Julian C Rayner, Rays H Y Jiang, John H Adams
Severe malaria is caused by the apicomplexan parasite Plasmodium falciparum. Despite decades of research, the distinct biology of these parasites has made it challenging to establish high-throughput genetic approaches to identify and prioritize therapeutic targets. Using transposon mutagenesis of P. falciparum in an approach that exploited its AT-rich genome, we generated more than 38,000 mutants, saturating the genome and defining mutability and fitness costs for over 87% of genes. Of 5399 genes, our study defined 2680 genes as essential for optimal growth of asexual blood stages in vitro...
May 4, 2018: Science
Pedro H Scarpelli Pereira, Chiara Curra, Celia R S Garcia
Parasites of Plasmodium genus are responsible for causing malaria in humans. Resistant strains to all available antimalarials can be found in several locations around the globe, including parasites resistant to the latest generation of combination drugs, such as piperaquine + artemisinin. Plasmodium develops between two completely different hosts such as a vertebrate one and the mosquito vector, thus it has the ability to adapt to very extreme and different environments. Through the complex life cycle in the hosts, Plasmodium invades and replicates in totally different cells thus making very difficult the study of the biology of the parasite and the identification of targets for drug development affecting all stages...
April 27, 2018: Current Topics in Medicinal Chemistry
Hyun Jae Lee, Athina Georgiadou, Thomas D Otto, Michael Levin, Lachlan J Coin, David J Conway, Aubrey J Cunnington
Transcriptomics, the analysis of genome-wide RNA expression, is a common approach to investigate host and pathogen processes in infectious diseases. Technical and bioinformatic advances have permitted increasingly thorough analyses of the association of RNA expression with fundamental biology, immunity, pathogenesis, diagnosis, and prognosis. Transcriptomic approaches can now be used to realize a previously unattainable goal, the simultaneous study of RNA expression in host and pathogen, in order to better understand their interactions...
June 2018: Microbiology and Molecular Biology Reviews: MMBR
Sergey Lunev, Sabine Butzloff, Atilio R Romero, Marleen Linzke, Fernando A Batista, Kamila A Meissner, Ingrid B Müller, Alaa Adawy, Carsten Wrenger, Matthew R Groves
Malaria remains a major threat to human health, as strains resistant to current therapeutics are discovered. Efforts in finding new drug targets are hampered by the lack of sufficiently specific tools to provide target validation prior to initiating expensive drug discovery projects. Thus, new approaches that can rapidly enable drug target validation are of significant interest. In this manuscript we present the crystal structure of malate dehydrogenase from Plasmodium falciparum (PfMDH) at 2.4 Å resolution and structure-based mutagenic experiments interfering with the inter-oligomeric interactions of the enzyme...
2018: PloS One
Amel Ghouila, Geoffrey Henry Siwo, Jean-Baka Domelevo Entfellner, Sumir Panji, Katrina A Button-Simons, Sage Zenon Davis, Faisal M Fadlelmola, Michael T Ferdig, Nicola Mulder
Scientific research plays a key role in the advancement of human knowledge and pursuit of solutions to important societal challenges. Typically, research occurs within specific institutions where data are generated and subsequently analyzed. Although collaborative science bringing together multiple institutions is now common, in such collaborations the analytical processing of the data is often performed by individual researchers within the team, with only limited internal oversight and critical analysis of the workflow prior to publication...
May 2018: Genome Research
Katelyn A Walzer, Danielle M Kubicki, Xiaohu Tang, Jen-Tsan Ashley Chi
Sexual reproduction is an obligate step in the Plasmodium falciparum life cycle, with mature gametocytes being the only form of the parasite capable of human-to-mosquito transmission. Development of male and female gametocytes takes 9 to 12 days, and although more than 300 genes are thought to be specific to gametocytes, only a few have been postulated to be male or female specific. Because these genes are often expressed during late gametocyte stages and for some, male- or female-specific transcript expression is debated, the separation of male and female populations is technically challenging...
April 25, 2018: MSphere
Yangmu Huang, Ke Pan, Danlu Peng, Andy Stergachis
BACKGROUND: While China is a major manufacturer of artemisinin and its derivatives, it lags as a global leader in terms of the total export value of anti-malarial drugs as finished pharmaceutical products ready for marketing and use by patients. This may be due to the limited number of World Health Organization (WHO) prequalified anti-malarial drugs from China. Understanding the reasons for the slow progress of WHO prequalification (PQ) in China can help improve the current situation and may lead to greater efforts in malaria eradication by Chinese manufacturers...
April 3, 2018: Malaria Journal
Gaoqian Feng, Michelle J Boyle, Nadia Cross, Jo-Anne Chan, Linda Reiling, Faith Osier, Danielle Stanisic, Ivo Mueller, Robin F Anders, James S McCarthy, Jack S Richards, James G Beeson
Background: Overcoming antigenic diversity is a key challenge in the development of effective P. falciparum malaria vaccines. Strategies that promote the generation of antibodies targeting conserved epitopes of vaccine antigens may provide protection against diverse parasites strains. Understanding differences between vaccine-induced and naturally-acquired immunity is important to achieving this goal. Methods: We analysed antibodies generated in a phase 1 human vaccine trial, MSP2-C1, which included two allelic forms MSP2, an abundant vaccine antigen on the merozoites surface...
March 23, 2018: Journal of Infectious Diseases
Joshua I Gray, Lotus M Westerhof, Megan K L MacLeod
Immunological memory provides rapid protection to pathogens previously encountered through infection or vaccination. CD4 T-cells play a central role in all adaptive immune responses. Vaccines must, therefore, activate CD4 T-cells if they are to generate protective immunity. For many diseases, we do not have effective vaccines. These include human immunodeficiency virus (HIV), tuberculosis and malaria, which are responsible for many millions of deaths each year across the globe. CD4 T-cells play many different roles during the immune response coordinating the actions of many other cells...
March 23, 2018: Immunology
Chalachew Alemayehu, Geoffrey Mitchell, Jane Nikles
BACKGROUND: Clinical trials for identification of efficient and effective new diagnostic and treatment modalities are needed to address disproportionately high burden of communicable (e.g., HIV/AIDS, tuberculosis, and malaria) and non-communicable diseases (e.g., diabetes) in developing countries. However, gross under-representation in global clinical trial platforms contributes to sustained health inequity in these countries. We reviewed the literature on barriers facing clinical researchers in developing countries for conducting clinical trials in their countries...
March 22, 2018: International Journal for Equity in Health
Sai Majji, Wathsala Wijayalath, Soumya Shashikumar, Teodor D Brumeanu, Sofia Casares
BACKGROUND: Human-immune-system humanized mouse models can bridge the gap between humans and conventional mice for testing human vaccines. The HLA-expressing humanized DRAGA (HLA-A2.HLA-DR4.Rag1KO.IL2RγcKO.NOD) mice reconstitute a functional human-immune-system and sustain the complete life cycle of Plasmodium falciparum. Herein, the DRAGA mice were investigated for immune responses following immunization with live P. falciparum sporozoites under chloroquine chemoprophylaxis (CPS-CQ), an immunization approach that showed in human trials to confer pre-erythrocytic immunity...
March 14, 2018: Malaria Journal
Cyrille Ndo, Edmond Kopya, Marie Agathe Donbou, Flobert Njiokou, Parfait Awono-Ambene, Charles Wondji
BACKGROUND: High coverage of long-lasting insecticidal nets (LLINs) is the cornerstone of the malaria control strategy of the national malaria control program (NMCP) in Cameroon, with a target of reducing malaria transmission to less than 10% by 2035. To this end, more than 20 million LLINs have been distributed to populations countrywide since 2011. The present study evaluated entomological indices and Anopheles susceptibility to pyrethroids in a rural forested area of south Cameroon with high coverage of LLINs...
March 8, 2018: Parasites & Vectors
Kunitaka Yoshida, Mitsuhiro Iyori, Andrew M Blagborough, Ahmed M Salman, Pawan Dulal, Katarzyna A Sala, Daisuke S Yamamoto, Shahid M Khan, Chris J Janse, Sumi Biswas, Tatsuya Yoshii, Yenni Yusuf, Masaharu Tokoro, Adrian V S Hill, Shigeto Yoshida
With the increasing prevalence of artemisinin-resistant malaria parasites, a highly efficacious and durable vaccine for malaria is urgently required. We have developed an experimental virus-vectored vaccine platform based on an envelope-modified baculovirus dual-expression system (emBDES). Here, we show a conceptually new vaccine platform based on an adenovirus-prime/emBDES-boost heterologous immunization regimen expressing the Plasmodium falciparum circumsporozoite protein (PfCSP). A human adenovirus 5-prime/emBDES-boost heterologous immunization regimen consistently achieved higher sterile protection against transgenic P...
March 1, 2018: Scientific Reports
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