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human malaria challenge

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...
April 12, 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 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
Johannes J Fagan
Surgeons in sub-Saharan Africa face different challenges than those in developed countries: extreme shortages of otolaryngologists, speech pathologists, and audiologists; lack of training opportunities; and a paucity of otolaryngology services aggravated by population growth and aging. In addition to common Western diseases, patients have otolaryngology complications related to the human immunodeficiency virus, tuberculosis, malaria, and trauma. Less than 5% of the population has access to timely, safe, affordable surgery; 29 out of 52 African countries have no radiotherapy services...
February 27, 2018: Otolaryngologic Clinics of North America
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
Aloysious Ssemaganda, Leanne M Low, Krista R Verhoeft, Mathias Wambuzi, Barbarah Kawoozo, Sharon B Nabasumba, Juliet Mpendo, Bernard S Bagaya, Noah Kiwanuka, Danielle I Stanisic, Susan J Berners-Price, Michael F Good
Here, the anti-malarial activity of two gold(i) phosphine compounds auranofin and [Au(d2pype)2 ]Cl (where d2pype is 1,2-bis(di-2-pyridylphosphino)ethane), were examined to inform their use as potential drugs and malaria parasite-attenuating agents. In vitro, the gold compounds were active against Plasmodium falciparum and P. knowlesi as well as the rodent parasite P. chabaudi AS. Attenuation of the parasite was observed when mice were inoculated with P. chabaudi AS infected red blood cells treated in vitro with [Au(d2pype)2 ]Cl (1 or 2 μM) or auranofin (2 μM) for 2 or 3 h...
February 21, 2018: Metallomics: Integrated Biometal Science
Rajagopal Murugan, Lisa Buchauer, Gianna Triller, Cornelia Kreschel, Giulia Costa, Gemma Pidelaserra Martí, Katharina Imkeller, Christian E Busse, Sumana Chakravarty, B Kim Lee Sim, Stephen L Hoffman, Elena A Levashina, Peter G Kremsner, Benjamin Mordmüller, Thomas Höfer, Hedda Wardemann
Affinity maturation, the clonal selection and expansion of antigen-activated B cells expressing somatically mutated antibody variants that develop during T cell-dependent germinal center reactions, is considered pivotal for efficient development of protective B cell memory responses to infection and vaccination. Repeated antigen exposure promotes affinity maturation but each time also recruits antigen-reactive naïve B cells into the response. Here, we determined the relative impact of affinity maturation versus antigen-mediated clonal selection of naïve B cells to mount potent B cell memory responses in humans after repeated exposure to a complex pathogen, the malaria parasite Plasmodium falciparum (Pf)...
February 16, 2018: Science Immunology
Konstantinos Mitsakakis, Sebastian Hin, Pie Müller, Nadja Wipf, Edward Thomsen, Michael Coleman, Roland Zengerle, John Vontas, Konstantinos Mavridis
Monitoring malaria prevalence in humans, as well as vector populations, for the presence of Plasmodium, is an integral component of effective malaria control, and eventually, elimination. In the field of human diagnostics, a major challenge is the ability to define, precisely, the causative agent of fever, thereby differentiating among several candidate (also non-malaria) febrile diseases. This requires genetic-based pathogen identification and multiplexed analysis, which, in combination, are hardly provided by the current gold standard diagnostic tools...
February 3, 2018: International Journal of Environmental Research and Public Health
Akram Abouie Mehrizi, Niloufar Rezvani, Sedigheh Zakeri, Atefeh Gholami, Laleh Babaeekhou
Malaria vaccine development has been confronted with various challenges such as poor immunogenicity of malaria vaccine candidate antigens, which is considered as the main challenge. However, this problem can be managed using appropriate formulations of antigens and adjuvants. Poly(I:C) is a potent Th1 inducer and a human compatible adjuvant capable of stimulating both B- and T-cell immunity. Plasmodium falciparum merozoite surface protein 142 (PfMSP-142) is a promising vaccine candidate for blood stage of malaria that has faced several difficulties in clinical trials, mainly due to improper adjuvants...
February 3, 2018: Medical Microbiology and Immunology
Michael F Good, Louis H Miller
Introduction As the quest for an effective blood stage malaria vaccine continues, there is increasing reliance on the use of controlled human malaria infections (CHMI) in non-endemic settings to test vaccine efficacy at the earliest possible time. This is seen as a way to accelerate vaccine research and quickly eliminate candidates with poor efficacy. Areas covered The data from these studies need to be carefully examined and interpreted in light of the very different roles that antibody and cellular immunity play in protection and within the context of the distinct clinical sensitivities of volunteers living in malaria-non-endemic countries compared to those living in endemic countries...
January 30, 2018: Expert Review of Vaccines
Suvitha Subramaniam, Christoph D Schmid, Xue Li Guan, Pascal Mäser
Combinatorial chemotherapy is imperative for the treatment of malaria. However, finding a suitable partner drug for a new candidate is challenging. Here we develop an algorithm that identifies all the gene pairs of Plasmodium falciparum which possess orthologues in yeast that have a synthetic lethal interaction, but are absent in humans. This suggests new options for drug combinations, in particular for inhibitors of targets like P. falciparum calcineurin, cation ATPase 4, or phosphatidylinositol 4-kinase.
January 22, 2018: Antimicrobial Agents and Chemotherapy
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
Emily Roggenkamp, Rachael M Giersch, Madison N Schrock, Emily Turnquist, Megan Halloran, Gregory C Finnigan
Control of biological populations is an ongoing challenge in many fields, including agriculture, biodiversity, ecological preservation, pest control, and the spread of disease. In some cases, such as insects that harbor human pathogens ( e.g. , malaria), elimination or reduction of a small number of species would have a dramatic impact across the globe. Given the recent discovery and development of the CRISPR-Cas9 gene editing technology, a unique arrangement of this system, a nuclease-based "gene drive," allows for the super-Mendelian spread and forced propagation of a genetic element through a population...
March 2, 2018: G3: Genes—Genomes—Genetics
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