101 results on '"PARASITOLOGY"'
Search Results
2. Deceiving and escaping complement – the evasive journey of the malaria parasite
- Author
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Maartje R. Inklaar, Carolina Barillas-Mury, and Matthijs M. Jore
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Infectious Diseases ,Anopheles ,Malaria Vaccines ,Plasmodium falciparum ,Animals ,Humans ,Parasites ,Parasitology ,Malaria - Abstract
During its life cycle, Plasmodium, the malaria parasite, is exposed to the human and mosquito complement systems. Early experiments demonstrated that activation of complement can pose a serious threat to parasites, but recent studies revealed complement-evasion mechanisms important for parasite survival. Blood-stage parasites and gametes recruit regulators to neutralize human complement activation, while ookinetes inhibit mosquito complement by disrupting epithelial nitration in response to midgut invasion. Here we provide an in-depth overview of the evasion mechanisms currently known and speculate on the existence of others not yet identified. Finally, we discuss how these mechanisms could provide novel targets for urgently needed malaria vaccines and therapeutics.
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- 2022
3. The ferredoxin redox system – an essential electron distributing hub in the apicoplast of Apicomplexa
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Sean Prigge, OJO AJOGU AKUH, Frank Seeber, and Rubayet Elahi
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Terpenes ,Iron ,Plasmodium falciparum ,Electrons ,Apicoplasts ,Infectious Diseases ,RNA, Transfer ,Ferredoxins ,Parasitology ,Apicomplexa ,Oxidation-Reduction ,Toxoplasma ,NADP ,Sulfur - Abstract
The apicoplast, a relict plastid found in most species of the phylum Apicomplexa, harbors the ferredoxin redox system which supplies electrons to enzymes of various metabolic pathways in this organelle. Recent reports in Toxoplasma gondii and Plasmodium falciparum have shown that the iron-sulfur cluster (FeS)-containing ferredoxin is essential in tachyzoite and blood-stage parasites, respectively. Here we review ferredoxin's crucial contribution to isoprenoid and lipoate biosynthesis as well as tRNA modification in the apicoplast, highlighting similarities and differences between the two species. We also discuss ferredoxin's potential role in the initial reductive steps required for FeS synthesis as well as recent evidence that offers an explanation for how NADPH required by the redox system might be generated in Plasmodium spp.
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- 2022
4. Evolving perspectives on rosetting in malaria
- Author
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Wenn-Chyau Lee, Bruce Russell, and Laurent Rénia
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Erythrocytes ,Rosette Formation ,Infectious Diseases ,Plasmodium falciparum ,Cell Adhesion ,Humans ,Parasitology ,Malaria, Falciparum ,Plasmodium vivax ,Malaria - Abstract
The ability of the intraerythrocytic Plasmodium spp. to form spontaneous rosettes with uninfected red blood cells (URBCs) has been observed in the medically important malaria parasites. Since the discovery of rosettes in the late 1980s, different formation mechanisms and pathobiological roles have been postulated for rosetting; most of which have focused on Plasmodium falciparum. Recent breakthroughs, including new data from Plasmodium vivax, have highlighted the multifaceted roles of rosetting in the immunopathobiology and the development of drug resistance in human malaria. Here, we provide new perspectives on the formation and the role of rosetting in malaria rheopathobiology.
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- 2022
5. Epigenetics of malaria parasite nutrient uptake, but why?
- Author
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Sanjay Desai
- Subjects
Plasmodium ,Erythrocytes ,Infectious Diseases ,Plasmodium falciparum ,Protozoan Proteins ,Animals ,Humans ,Parasitology ,Nutrients ,Malaria, Falciparum ,Epigenesis, Genetic ,Malaria - Abstract
The conserved plasmodial surface anion channel (PSAC) mediates nutrient uptake by bloodstream malaria parasites and is an antimalarial target. This pathogen-associated channel is linked to the clag multigene family, which is variably expanded in Plasmodium spp. Member genes are under complex epigenetic regulation, with the clag3 genes of the human P. falciparum pathogen exhibiting monoallelic transcription and mutually exclusive surface exposure on infected erythrocytes. While other multigene families use monoallelic expression to evade host immunity, the reasons of epigenetic control of clag genes are unclear. I consider existing models and their implications for nutrient acquisition and immune evasion. Understanding the reasons for epigenetic regulation of PSAC-mediated nutrient uptake will help clarify host-pathogen interactions and guide development of therapies resistant to allele switching.
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- 2022
6. The assessment of antimalarial drug efficacy in vivo
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Nicholas White
- Subjects
Antimalarials ,Infectious Diseases ,Plasmodium falciparum ,Drug Resistance ,Malaria, Vivax ,Humans ,Parasitology ,Malaria, Falciparum ,Parasitemia ,Plasmodium vivax ,Malaria - Abstract
Currently recommended methods of assessing the efficacy of uncomplicated falciparum malaria treatment work less well in high-transmission than in low-transmission settings. There is also uncertainty how to assess intermittent preventive therapies and seasonal malaria chemoprevention (SMC), and Plasmodium vivax radical cure. A pharmacometric antimalarial resistance monitoring (PARM) approach is proposed specifically for evaluating slowly eliminated antimalarial drugs in areas of high transmission. In PARM antimalarial drug concentrations at recurrent parasitaemia are measured to identify outliers (i.e., recurrent parasitaemias in the presence of normally suppressive drug concentrations) and to evaluate changes over time. PARM requires characterization of pharmacometric profiles but should be simpler and more sensitive than current molecular genotyping-based methodologies. PARM does not require parasite genotyping and can be applied to the assessment of both prevention and treatment.
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- 2022
7. Malaria artemisinin resistance: an extracellular vesicles export hypothesis
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Kwesi Zandoh Tandoh, Nancy Duah-Quashie, NEILS QUASHIE, Michael Wilson, and Collins Morang'a
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Antimalarials ,Extracellular Vesicles ,Infectious Diseases ,Plasmodium falciparum ,Drug Resistance ,Humans ,Parasitology ,Malaria, Falciparum ,Artemisinins ,Malaria - Abstract
Plasmodium falciparum causes malaria, and its resistance to artemisinin (ART) - a drug used for managing malaria - threatens to interfere with the effective control of malaria. ART resistance (ARTr) is driven by increased tolerance to oxidative stress and reduced haemoglobin trafficking to the food vacuole. We discuss how extracellular vesicles (EVs) may play a role in developing ARTr.
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- 2022
8. Housebreaking Plasmodium parasites leave their fingerprints at the door
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Lara Bardtke and Ian A. Cockburn
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Erythrocytes ,Infectious Diseases ,Malaria Vaccines ,Plasmodium falciparum ,Protozoan Proteins ,Animals ,Antibodies, Protozoan ,Antigens, Protozoan ,Parasites ,Parasitology ,Malaria, Falciparum - Abstract
Protective antibodies against Plasmodium falciparum merozoite antigens, including EBA-175, can inhibit erythrocyte invasion. New data from Musasia et al. indicate that these antibodies can also trigger antibody-dependent phagocytosis of ring-infected and uninfected erythrocytes and that this correlates with protection from malaria. This provides a new pathway for vaccine design.
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- 2022
9. Leveraging genome editing to functionally evaluate Plasmodium diversity
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Laty Gaye Thiam, Alassane Mbengue, Aboubacar BA, Khadidiatou Mangou, and Amy Bei
- Subjects
Gene Editing ,Plasmodium ,Infectious Diseases ,Plasmodium falciparum ,Humans ,Parasitology ,Malaria, Falciparum ,Malaria - Abstract
The ambitious goal of malaria elimination requires an in-depth understanding of the parasite's biology to counter the growing threat of antimalarial resistance and immune evasion. Timely assessment of the functional impact of antigenic diversity in the early stages of vaccine development will be critical for achieving the goal of malaria control, elimination, and ultimately eradication. Recent advances in targeted genome editing enabled the functional validation of resistance-associated markers in Plasmodium falciparum, the deadliest malaria-causing pathogen and strain-specific immune neutralization. This review explores recent advances made in leveraging genome editing to aid the functional evaluation of Plasmodium diversity and highlights how these techniques can assist in prioritizing both therapeutic and vaccine candidates.
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- 2022
10. Potential pharmacologic interventions targeting TLR signaling in placental malaria
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Francis M. Kobia, Kaushik Maiti, Moses M. Obimbo, Roger Smith, and Jesse Gitaka
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Infectious Diseases ,Pregnancy ,Placenta ,Pregnancy Complications, Parasitic ,Plasmodium falciparum ,Infant, Newborn ,Humans ,Female ,Parasitology ,Malaria, Falciparum ,Article ,Malaria - Abstract
Complications from placental malaria cause poor pregnancy outcomes, including low birthweight, preterm delivery, and stillbirths. Many of these complications are driven by maternal innate proinflammatory responses to the sequestration of Plasmodium falciparum in the placenta. However, recent studies show that, in reaction to maternal innate immune responses that are detrimental to the fetus, the fetus mounts innate immune counter-responses that ameliorate pregnancy outcomes. Such fetal-maternal conflict in placental malaria has potential for pharmacologic modulation for better pregnancy outcomes. Here, we discuss placental malaria pathogenesis, its complications, and the role of innate immunity and fetal-maternal innate immune conflict in placental malaria. Finally, we discuss pharmacologic immunomodulatory strategies and agents with the potential to improve placental malaria outcomes.
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- 2022
11. Plasmodium’s bottomless pit: properties and functions of the malaria parasite's digestive vacuole
- Author
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Joachim Michael Matz
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Antimalarials ,Hemoglobins ,Infectious Diseases ,Plasmodium falciparum ,Vacuoles ,Animals ,Humans ,Parasites ,Parasitology ,Heme ,Malaria - Abstract
During intraerythrocytic growth, the human malaria parasite Plasmodium falciparum degrades up to 80% of the host cell's hemoglobin inside an acidified organelle called the digestive vacuole (DV). Here, the globin chains are broken down by a number of proteases, while heme is detoxified through biomineralization, a process that is targeted by several potent antimalarial drugs. This review explores our current understanding of the DV, including the digestion of hemoglobin, the sequestration of heme, and the functions of lipids and transporters of the DV membrane. Furthermore, the mechanisms of drug action inside the DV and the molecular adaptations that mediate resistance are discussed.
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- 2022
12. Malaria parasites do respond to heat
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Elisabet Tintó-Font and Alfred Cortes
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Infectious Diseases ,Plasmodium falciparum ,Protozoan Proteins ,Animals ,Parasites ,Parasitology ,Malaria, Falciparum ,Malaria ,Transcription Factors - Abstract
The capacity of malaria parasites to respond to changes in their environment at the transcriptional level has been the subject of debate, but recent evidence has unambiguously demonstrated that Plasmodium spp. can produce adaptive transcriptional responses when exposed to some specific types of stress. These include metabolic conditions and febrile temperature. The Plasmodium falciparum protective response to thermal stress is similar to the response in other organisms, but it is regulated by a transcription factor evolutionarily unrelated to the conserved transcription factor that drives the heat shock (HS) response in most eukaryotes. Of the many genes that change expression during HS, only a subset constitutes an authentic response that contributes to parasite survival.
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- 2022
13. No sweet deal: the antibody-mediated immune response to malaria
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Gestur Vidarsson, Lars Hviid, Mary Lopez-Perez, and Mads Larsen
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Plasmodium falciparum malaria ,Erythrocytes ,Fc region ,Fcγ receptors ,Plasmodium falciparum ,Protozoan Proteins ,Antibodies, Protozoan ,Antigens, Protozoan ,Adaptive Immunity ,antibody effector function ,acquired immunity ,Infectious Diseases ,Immunoglobulin G ,parasitic diseases ,fucosylation ,Humans ,Parasitology ,Malaria, Falciparum - Abstract
IgG antibodies are key effector molecules in acquired immunity to Plasmodium falciparum malaria, and the PfEMP1 adhesins expressed on the surface of the infected erythrocytes are crucial immunological targets. The antigen specificity of these antibodies has therefore been a major research focus. However, we recently reported that the Fc domain of naturally induced PfEMP1-specific IgG1 is selectively modified by post-translational omission of fucose from the conserved Fc glycan. The resulting afucosylated IgG has increased affinity for the IgG-Fc-receptor III family (FcγRIII), found on natural killer cells and on subsets of other cells in the immune system. We discuss the implications of these findings for the basic understanding of antimalarial immunity and for the design of improved vaccines against the disease.
- Published
- 2022
14. Thwarting protein synthesis leads to malaria parasite paralysis
- Author
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Godfrey Mayoka, John G. Woodland, and Kelly Chibale
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Antimalarials ,Infectious Diseases ,Plasmodium falciparum ,Animals ,Humans ,Paralysis ,Tyrosine ,Parasites ,Parasitology ,Malaria, Falciparum ,Malaria - Abstract
Inhibiting translation presents a tantalizing strategy to tackle the most virulent human malaria parasite. Xie et al. disclose a compound that binds selectively to Plasmodium falciparum tyrosine aminoacyl-tRNA synthetase, preventing the incorporation of tyrosine into nascent proteins and paving the way for a new generation of safe, effective antimalarials.
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- 2022
15. Falciparum malaria mortality in sub-Saharan Africa in the pretreatment era
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Arjen M. Dondorp, Nicholas J. White, James A Watson, and Intensive Care Medicine
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Sub saharan ,Plasmodium falciparum ,Balancing selection ,Sickle Cell Trait ,law.invention ,sickle cell ,law ,parasitic diseases ,medicine ,Humans ,Malaria, Falciparum ,hemoglobin S ,Child ,Allele frequency ,Africa South of the Sahara ,Hemoglobin s ,biology ,malaria-attributable mortality ,biology.organism_classification ,medicine.disease ,Malaria ,Infectious Diseases ,Transmission (mechanics) ,falciparum malaria ,Parasitology ,Demography - Abstract
Driven by the malaria-protective effect of sickle-cell trait, balancing selection results in hemoglobin S equilibrium allele frequencies of between 15% and 20% in areas of high Plasmodium falciparum transmission in sub-Saharan Africa. From this we estimate that the malaria-attributable childhood mortality in the pretreatment era was between 15% and 24%.
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- 2022
16. Deconstructing the parasite multiplication rate of Plasmodium falciparum
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Caroline O. Buckee, Bénédicte Gnangnon, and Manoj T. Duraisingh
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0301 basic medicine ,Erythrocytes ,Plasmodium falciparum ,030231 tropical medicine ,Protozoan Proteins ,Host factors ,Plasmodium ,Epidemiological indicators ,Host-Parasite Interactions ,03 medical and health sciences ,0302 clinical medicine ,Malaria transmission ,Environmental health ,parasitic diseases ,medicine ,Animals ,Humans ,Parasite hosting ,Malaria, Falciparum ,biology ,Multiplication rate ,biology.organism_classification ,medicine.disease ,030104 developmental biology ,Infectious Diseases ,Parasitology ,Malaria - Abstract
Epidemiological indicators describing population-level malaria transmission dynamics are widely used to guide policy recommendations. However, the determinants of malaria outcomes within individuals are still poorly understood. This conceptual gap partly reflects the fact that there are few indicators that robustly predict the trajectory of individual infections or clinical outcomes. The parasite multiplication rate (PMR) is a widely used indicator for the Plasmodium intraerythrocytic development cycle (IDC), for example, but its relationship to clinical outcomes is complex. Here, we review its calculation and use in P. falciparum malaria research, as well as the parasite and host factors that impact it. We also provide examples of metrics that can help to link within-host dynamics to malaria clinical outcomes when used alongside the PMR.
- Published
- 2021
17. Defining the Essential Exportome of the Malaria Parasite
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Thorey K Jonsdottir, Brendan S. Crabb, Mikha Gabriela, Tania F. de Koning-Ward, and Paul R. Gilson
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0301 basic medicine ,Plasmodium falciparum ,030231 tropical medicine ,Protozoan Proteins ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Animals ,Humans ,Parasite hosting ,Genetic Testing ,Genetics ,biology ,Host (biology) ,medicine.disease ,biology.organism_classification ,Malaria ,Protein Transport ,030104 developmental biology ,Infectious Diseases ,Host-Pathogen Interactions ,Parasitology ,Genetic screen - Abstract
To survive inside red blood cells (RBCs), malaria parasites export many proteins to alter their host cell's physiological properties. Although most proteins of this exportome are involved in immune avoidance or in the trafficking of exported proteins to the host membrane, about 20% are essential for parasite survival in culture but little is known about their biological functions. Here, we have combined information from large-scale genetic screens and targeted gene-disruption studies to tabulate all currently known Plasmodium falciparum exported proteins according to their likelihood of being essential. We also discuss the essential functional pathways that exported proteins might be involved in to help direct research efforts towards a more comprehensive understanding of host-cell remodelling.
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- 2021
18. Genomic and Genetic Approaches to Studying Antimalarial Drug Resistance and Plasmodium Biology
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David A. Fidock, Mariko Kanai, John Okombo, and Ioanna Deni
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0301 basic medicine ,medicine.medical_specialty ,Plasmodium falciparum ,030231 tropical medicine ,Drug Resistance ,Genomics ,Drug resistance ,Computational biology ,Biology ,Genome ,Article ,Antimalarials ,03 medical and health sciences ,0302 clinical medicine ,Genome editing ,Molecular genetics ,parasitic diseases ,medicine ,Humans ,Malaria, Falciparum ,Molecular Biology ,Gene ,Drug discovery ,biology.organism_classification ,030104 developmental biology ,Infectious Diseases ,Parasitology ,Genome, Protozoan - Abstract
Recent progress in genomics and molecular genetics has empowered novel approaches to closely study gene functions in disease-causing pathogens. In the human malaria parasite Plasmodium falciparum, the application of genome-based analyses, site-directed genome editing, and genetic systems that allow for temporal and quantitative regulation of gene and protein expression have been invaluable in defining the genetic basis of antimalarial resistance and elucidating candidate targets to accelerate drug discovery efforts. Using examples from recent studies, we review applications of some of these approaches in advancing our understanding of Plasmodium biology and illustrate their contributions and limitations in characterizing parasite genomic loci associated with antimalarial drug responses.
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- 2021
19. Parasite and Host Erythrocyte Kinomics of Plasmodium Infection
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Christian Doerig, Tayla Williamson, and Jack D. Adderley
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0301 basic medicine ,Erythrocytes ,Plasmodium falciparum ,030106 microbiology ,Protozoan Proteins ,Context (language use) ,Drug resistance ,Plasmodium ,Host-Parasite Interactions ,Antimalarials ,03 medical and health sciences ,parasitic diseases ,medicine ,Humans ,Parasite hosting ,Kinome ,biology ,Kinase ,biology.organism_classification ,medicine.disease ,Virology ,Malaria ,030104 developmental biology ,Infectious Diseases ,Parasitology ,Protein Kinases - Abstract
Malaria remains a heavy public health and socioeconomic burden in tropical and subtropical regions. Increasing resistance against front-line treatments implies that novel targets for antimalarial intervention are urgently required. Protein kinases of both the parasites and their host cells possess strong potential in this respect. We present an overview of the updated kinome of Plasmodium falciparum, the species that is the largest contributor to malaria mortality, and of current knowledge pertaining to the function of parasite-encoded protein kinases during the parasite's life cycle. Furthermore, we detail recent advances in drug initiatives targeting Plasmodium kinases and outline the potential of protein kinases in the context of the growing field of host-directed therapies, which is currently being explored as a novel way to combat parasite drug resistance.
- Published
- 2021
20. Bioengineered 3D Microvessels for Investigating Plasmodium falciparum Pathogenesis
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Maria Bernabeu, Joseph D. Smith, Caitlin C. Howard, and Ying Zheng
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0301 basic medicine ,Plasmodium falciparum ,030231 tropical medicine ,Bioengineering ,Disease ,Article ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,parasitic diseases ,medicine ,Animals ,Humans ,Tropism ,Causal pathways ,biology ,Brain ,biology.organism_classification ,medicine.disease ,030104 developmental biology ,Infectious Diseases ,Cerebral Malaria ,Microvessels ,Parasitology ,Neuroscience ,Malaria - Abstract
Plasmodium falciparum pathogenesis is complex and intimately connected to vascular physiology. This is exemplified by cerebral malaria (CM), a neurovascular complication that accounts for most of the malaria deaths worldwide. P. falciparum sequestration in the brain microvasculature is a hallmark of CM and is not replicated in animal models. Numerous aspects of the disease are challenging to fully understand from clinical studies, such as parasite binding tropism or causal pathways in blood-brain barrier breakdown. Recent bioengineering approaches allow for the generation of 3D microvessels and organ-specific vasculature that provide precise control of vessel architecture and flow dynamics, and hold great promise for malaria research. Here, we discuss recent and future applications of bioengineered microvessels in malaria pathogenesis research.
- Published
- 2021
21. There and back again: malaria parasite single-cell transcriptomics comes full circle
- Author
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Björn F.C. Kafsack and Christopher Nötzel
- Subjects
Male ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Single cell transcriptomics ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Plasmodium falciparum ,Mosquito Vectors ,Article ,Host-Parasite Interactions ,law.invention ,Antimalarials ,Species Specificity ,law ,Anopheles ,parasitic diseases ,medicine ,Animals ,Humans ,Parasite hosting ,RNA-Seq ,Malaria, Falciparum ,Life Cycle Stages ,biology ,medicine.disease ,biology.organism_classification ,Virology ,Infectious Diseases ,Transmission (mechanics) ,Female ,Parasitology ,Single-Cell Analysis ,Transcriptome ,Malaria - Abstract
Malaria parasites have a complex life cycle featuring diverse developmental strategies, each uniquely adapted to navigate specific host environments. Here we use single-cell transcriptomics to illuminate gene usage across the transmission cycle of the most virulent agent of human malaria - Plasmodium falciparum. We reveal developmental trajectories associated with the colonization of the mosquito midgut and salivary glands and elucidate the transcriptional signatures of each transmissible stage. Additionally, we identify both conserved and non-conserved gene usage between human and rodent parasites, which point to both essential mechanisms in malaria transmission and species-specific adaptations potentially linked to host tropism. Together, the data presented here, which are made freely available via an interactive website, provide a fine-grained atlas that enables intensive investigation of the P. falciparum transcriptional journey. As well as providing insights into gene function across the transmission cycle, the atlas opens the door for identification of drug and vaccine targets to stop malaria transmission and thereby prevent disease.
- Published
- 2021
22. Triple Artemisinin-Based Combination Therapies for Malaria – A New Paradigm?
- Author
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Mehul Dhorda, Chanaki Amaratunga, Rob W. van der Pluijm, and Arjen M. Dondorp
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0301 basic medicine ,Drug ,Artemisinins ,medicine.medical_specialty ,media_common.quotation_subject ,Plasmodium falciparum ,030231 tropical medicine ,malaria ,Drug Resistance ,Drug resistance ,P. falciparum ,resistance ,Antimalarials ,03 medical and health sciences ,0302 clinical medicine ,parasitic diseases ,medicine ,Humans ,Malaria, Falciparum ,Available drugs ,Artemisinin ,Intensive care medicine ,TACT ,Asia, Southeastern ,media_common ,biology ,business.industry ,biology.organism_classification ,medicine.disease ,ACT ,030104 developmental biology ,Infectious Diseases ,artemisinin ,Drug Therapy, Combination ,Parasitology ,business ,Malaria ,medicine.drug - Abstract
Recent gains in the fight against malaria are threatened by the emergence and spread of artemisinin and partner drug resistance in Plasmodium falciparum in the Greater Mekong Subregion (GMS). When artemisinins are combined with a single partner drug, all recommended artemisinin-based combination therapies have shown reduced efficacy in some countries in the GMS at some point. Novel drugs are not available for the near future. Triple artemisinin-based combination therapies, combining artemisinins with two currently available partner drugs, will provide one of the last remaining safe and effective treatments for falciparum malaria that can be deployed rapidly in the GMS, whereas their deployment beyond the GMS could delay or prevent the global emergence and spread of resistance to currently available drugs.
- Published
- 2021
23. Antibody Therapy Goes to Insects: Monoclonal Antibodies Can Block Plasmodium Transmission to Mosquitoes
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Camila H. Coelho, Teun Bousema, Gaspar E. Canepa, Carolina Barillas-Mury, Patrick E. Duffy, and Matthijs M. Jore
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0301 basic medicine ,medicine.drug_class ,Plasmodium falciparum ,030231 tropical medicine ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Monoclonal antibody ,Plasmodium ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,parasitic diseases ,medicine ,Animals ,Humans ,Parasite hosting ,Disease Eradication ,Life Cycle Stages ,biology ,Transmission (medicine) ,Antibodies, Monoclonal ,medicine.disease ,biology.organism_classification ,Virology ,Malaria ,Culicidae ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,030104 developmental biology ,Infectious Diseases ,Parasitology ,Antibody therapy - Abstract
Contains fulltext : 229558.pdf (Publisher’s version ) (Closed access) Malaria eradication is a global priority but requires innovative strategies. Humoral immune responses attack different parasite stages, and antibody-based therapy may prevent malaria infection or transmission. Here, we discuss targets of monoclonal antibodies in mosquito sexual stages of Plasmodium.
- Published
- 2020
24. Optimizing Plasmodium vivax serological surveillance within a coendemic epidemiological landscape
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Regina Joice Cordy and Amy Bei
- Subjects
Infectious Diseases ,Plasmodium falciparum ,Malaria, Vivax ,Humans ,Parasitology ,Malaria, Falciparum ,Plasmodium vivax ,Malaria - Abstract
Serological surveillance is a useful tool for revealing hotspots of transmission intensity or cryptic asymptomatic reservoirs, especially as malaria transmission declines. Such approaches can help us to understand malaria epidemiology, but also to guide interventions. Recently, Longley et al. refined a panel for Plasmodium vivax serological surveillance to aid in malaria elimination.
- Published
- 2022
25. In vitro models for human malaria: targeting the liver stage
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Ana Lisa Valenciano, Maria G. Gomez-Lorenzo, Joel Vega-Rodríguez, John H. Adams, and Alison Roth
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Antimalarials ,Life Cycle Stages ,Plasmodium ,Infectious Diseases ,Liver ,Plasmodium falciparum ,Animals ,Humans ,Parasitology ,Malaria - Abstract
The Plasmodium liver stage represents a vulnerable therapeutic target to prevent disease progression as the parasite resides in the liver before clinical representation caused by intraerythrocytic development. However, most antimalarial drugs target the blood stage of the parasite's life cycle, and the few drugs that target the liver stage are lethal to patients with a glucose-6-phosphate dehydrogenase deficiency. Furthermore, implementation of in vitro liver models to study and develop novel therapeutics against the liver stage of human Plasmodium species remains challenging. In this review, we focus on the progression of in vitro liver models developed for human Plasmodium spp. parasites, provide a brief review on important assay requirements, and lastly present recommendations to improve models to enhance the discovery process of novel preclinical therapeutics.
- Published
- 2022
26. Humanized Mice and the Rebirth of Malaria Genetic Crosses
- Author
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Katelyn M. Vendrely, Ashley M. Vaughan, Xue Li, and Sudhir Kumar
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0301 basic medicine ,Plasmodium falciparum ,030231 tropical medicine ,Virulence ,Article ,law.invention ,Mice ,03 medical and health sciences ,0302 clinical medicine ,law ,Genetic linkage ,Genotype ,medicine ,Animals ,Humans ,Parasite hosting ,Malaria, Falciparum ,Crosses, Genetic ,Genetics ,Cloning ,biology ,medicine.disease ,biology.organism_classification ,030104 developmental biology ,Infectious Diseases ,Recombinant DNA ,Parasitology ,Malaria - Abstract
The first experimental crosses carried out with the human malaria parasite Plasmodium falciparum played a key role in determining the genetic loci responsible for drug resistance, virulence, invasion, growth rate, and transmission. These crosses relied on splenectomized chimpanzees to complete the liver stage of the parasite's life cycle and the subsequent transition to asexual blood stage culture followed by cloning of recombinant progeny in vitro. Crosses can now be routinely carried out using human-liver-chimeric mice infused with human erythrocytes to generate hundreds of unique recombinant progeny for genetic linkage mapping, bulk segregant analysis, and high-throughput 'omics readouts. The high number of recombinant progeny should allow for unprecedented power and efficiency in the execution of a systems genetics approach to study P. falciparum biology.
- Published
- 2020
27. Plasmodium vivax in the Era of the Shrinking P. falciparum Map
- Author
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Katherine E. Battle, Kamala Thriemer, Ric N. Price, Robert J. Commons, and Kamini N. Mendis
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0301 basic medicine ,Primaquine ,Plasmodium falciparum ,030231 tropical medicine ,Plasmodium vivax ,Biology ,Article ,Antimalarials ,03 medical and health sciences ,0302 clinical medicine ,parasitic diseases ,Malaria, Vivax ,medicine ,Animals ,Humans ,Disease Eradication ,Malaria, Falciparum ,Transmission (medicine) ,Incidence ,Incidence (epidemiology) ,biology.organism_classification ,Key features ,medicine.disease ,Virology ,030104 developmental biology ,Infectious Diseases ,Parasitology ,Malaria ,medicine.drug - Abstract
Plasmodium vivax is an important cause of malaria, associated with a significant public health burden. Whilst enhanced malaria-control activities have successfully reduced the incidence of Plasmodium falciparum malaria in many areas, there has been a consistent increase in the proportion of malaria due to P. vivax in regions where both parasites coexist. This article reviews the epidemiology and biology of P. vivax, how the parasite differs from P. falciparum, and the key features that render it more difficult to control and eliminate. Since transmission of the parasite is driven largely by relapses from dormant liver stages, its timely elimination will require widespread access to safe and effective radical cure.
- Published
- 2020
28. Vive la Différence: Exploiting the Differences between Rodent and Human Malarias
- Author
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Laura A. Kirkman and Kirk W. Deitsch
- Subjects
0301 basic medicine ,Plasmodium ,Rodent ,030231 tropical medicine ,Rodentia ,Article ,Host-Parasite Interactions ,03 medical and health sciences ,0302 clinical medicine ,Animal model ,Human disease ,biology.animal ,parasitic diseases ,medicine ,Animals ,Humans ,biology ,Rodent model ,Plasmodium falciparum ,biology.organism_classification ,medicine.disease ,Experimental research ,Malaria ,Disease Models, Animal ,030104 developmental biology ,Infectious Diseases ,Evolutionary biology ,Human parasite ,Parasitology - Abstract
Experimental research into malaria biology and pathogenesis has historically focused on two model systems, in vitro culture of the human parasite Plasmodium falciparum and in vivo infections of laboratory animals using rodent parasites. While there is clear value in having a manipulatable animal model for studying malaria, there have occasionally been controversies around how representative the rodent model is of the human disease, and therefore significant emphasis has been placed on the similarities between the two biological systems. By focusing on basic nuclear functions, we wish to highlight that identifying key differences in the parasites and their interactions with their mammalian hosts can be equally informative and provide remarkable insights into the biology and evolution of these important infectious organisms.
- Published
- 2020
29. K13, the Cytostome, and Artemisinin Resistance
- Author
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Leann Tilley, Stanley C. Xie, and Stuart A. Ralph
- Subjects
0301 basic medicine ,Plasmodium ,Artemisinins ,030231 tropical medicine ,Drug Resistance ,Protozoan Proteins ,Heme ,Drug resistance ,medicine.disease_cause ,Antimalarials ,03 medical and health sciences ,0302 clinical medicine ,parasitic diseases ,medicine ,Humans ,Artemisinin ,Mutation ,biology ,Plasmodium falciparum ,medicine.disease ,biology.organism_classification ,Virology ,030104 developmental biology ,Infectious Diseases ,Parasitology ,Malaria ,medicine.drug ,Cytostome - Abstract
Artemisinins - the frontline antimalarial drug class - are compromised by emerging resistance, putting at risk the lives of hundreds of thousands of people each year. Resistance is associated with mutations in a malaria parasite protein, called Kelch 13 (K13). Recent work suggests that K13 is located at the cytostome (cell mouth) that the parasite uses to take up hemoglobin. Here we explore the proposal that K13 mutations confer artemisinin resistance by dampening hemoglobin endocytosis. This model suggests that the resultant decrease in hemoglobin-derived heme reduces artemisinin activation, which is sufficient to enable parasite survival in the early ring stage of infection. A fuller understanding of the resistance mechanism will underpin efforts to develop alternative antimalarial strategies.
- Published
- 2020
30. The RH5-CyRPA-Ripr Complex as a Malaria Vaccine Target
- Author
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Matthew K. Higgins, Simon J. Draper, and Robert J. Ragotte
- Subjects
malaria vaccine ,0301 basic medicine ,Plasmodium falciparum ,030231 tropical medicine ,Protozoan Proteins ,Antigens, Protozoan ,erythrocyte invasion ,Disease ,Article ,03 medical and health sciences ,CyRPA ,0302 clinical medicine ,Malaria Vaccines ,parasitic diseases ,Medicine ,Ripr ,Clinical Trials as Topic ,biology ,business.industry ,Malaria vaccine ,biology.organism_classification ,Antibodies, Neutralizing ,Virology ,Malaria ,3. Good health ,Clinical trial ,Blood stage ,RH5 ,030104 developmental biology ,Infectious Diseases ,Parasitology ,Carrier Proteins ,business - Abstract
Despite ongoing efforts, a highly effective vaccine against Plasmodium falciparum remains elusive. Vaccines targeting the pre-erythrocytic stages of the P. falciparum life cycle are the most advanced to date, affording moderate levels of efficacy in field trials. However, the discovery that the members of the merozoite PfRH5-PfCyRPA-PfRipr (RCR) complex are capable of inducing strain-transcendent neutralizing antibodies has renewed enthusiasm for the possibility of preventing disease by targeting the parasite during the blood stage of infection. With Phase I/II clinical trials now underway using first-generation vaccines against PfRH5, and more on the horizon for PfCyRPA and PfRipr, this review explores the rationale and future potential of the RCR complex as a P. falciparum vaccine target., Highlights The antigens PfRH5, PfCyRPA, and PfRipr can induce strain-transcendent neutralizing antibodies, and all three targets are essential and highly conserved. PfRH5, PfCyRPA, and PfRipr form a stable complex (RCR) that is involved in the induction of an erythrocytic calcium spike during merozoite invasion. Passive transfer of anti-CyRPA and anti-PfRH5 antibodies can protect against blood-stage P. falciparum in animal models. Structural studies have mapped out the first known critical inhibitory epitopes on PfRH5 and PfCyRPA which can be used for next-generation vaccine design. Early results from the first PfRH5 vaccine clinical trials have been reported with more anticipated soon, which will help guide the development of RCR-based vaccines.
- Published
- 2020
31. Malaria Parasite Clearance: What Are We Really Measuring?
- Author
-
James McCarthy, Miles Davenport, Sophie Zaloumis, Maria Rebelo, Matthew Joseph Grigg, David Khoury, and Jennifer Flegg
- Subjects
0301 basic medicine ,Drug ,medicine.medical_specialty ,media_common.quotation_subject ,Plasmodium falciparum ,030231 tropical medicine ,Parasitemia ,Efficacy ,Antimalarials ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Malaria, Falciparum ,Intensive care medicine ,media_common ,business.industry ,Optimal treatment ,medicine.disease ,Clinical trial ,Treatment Outcome ,030104 developmental biology ,Infectious Diseases ,Drug activity ,Drug development ,Parasitology ,business ,Malaria - Abstract
Antimalarial drugs are vital for treating malaria and controlling transmission. Measuring drug efficacy in the field requires large clinical trials and thus we have identified proxy measures of drug efficacy such as the parasite clearance curve. This is often assumed to measure the rate of drug activity against parasites and is used to predict optimal treatment regimens required to completely clear a blood-stage infection. We discuss evidence that the clearance curve is not measuring the rate of drug killing. This has major implications for how we assess optimal treatment regimens, as well as how we prioritise new drugs in the drug development pipeline.
- Published
- 2020
32. Can malaria parasites be spontaneously cleared?
- Author
-
Merryn S. Roe, Katherine O’Flaherty, and Freya J.I. Fowkes
- Subjects
Antimalarials ,Infectious Diseases ,Plasmodium falciparum ,Animals ,Parasitology ,Parasites ,Malaria, Falciparum ,Malaria - Abstract
A large body of evidence demonstrates that Plasmodium falciparum infections are chronic in malaria endemic areas; however, the notion of spontaneous clearance in the absence of antimalarial drug treatment is rarely discussed. In this opinion article, we review and reinterpret data to postulate that spontaneous clearance of P. falciparum infections occurs frequently, has been demonstrated in a range of transmission settings, and confirmed by the most sensitive malaria diagnostic techniques. We also discuss factors which may influence the likelihood, measurement, and conclusions of spontaneous clearance. A greater understanding of the phenomenon of spontaneous clearance will advance our knowledge of malaria epidemiology, transmission potential of malaria parasites, as well as inform interventions for malaria control and elimination.
- Published
- 2021
33. Transmission-blocking drugs for malaria elimination
- Author
-
Lyn-Marié Birkholtz, Pietro Alano, and Didier Leroy
- Subjects
Antimalarials ,Life Cycle Stages ,Infectious Diseases ,Plasmodium falciparum ,Drug Resistance ,Animals ,Humans ,Parasitology ,Malaria, Falciparum ,Malaria - Abstract
Preventing human-to-mosquito transmission of malaria parasites provides possible solutions to interrupt the malaria parasite life cycle for malaria elimination. The development of validated routine assays enabled the discovery of such transmission-blocking compounds. Currently, one development priority remains on combinations of dual-active compounds with equipotent activity against both the disease-causing asexual and transmissible, sexual erythrocytic stages. Additionally, transmission-blocking compounds that target gametocyte-specific biology could be used in combination with compounds against asexual parasites. In either case, preventing transmission will reduce the risk of reinfection and, if different processes are targeted, also curb the spread of drug resistance. Here, we provide an updated roadmap to the discovery and development of new antimalarials with transmission-blocking activity to guide drug discovery for malaria elimination.
- Published
- 2021
34. Affinity-purified Plasmodium tubulin provides a key reagent for antimalarial drug development
- Author
-
Scott Dawson and Shane McInally
- Subjects
Antimalarials ,Infectious Diseases ,Tubulin ,Plasmodium falciparum ,Animals ,Indicators and Reagents ,Parasites ,Parasitology - Abstract
Hirst et al. used a TOG-domain-based affinity-purification approach to reconstitute and define the in vitro dynamics of blood-stage Plasmodium falciparum αβ-tubulin. This provides a key reagent for defining parasite microtubule (MT) dynamics and for evaluating the efficacy of anti-MT drugs throughout the complex parasite life cycle.
- Published
- 2022
35. RBC membrane biomechanics and Plasmodium falciparum invasion: probing beyond ligand-receptor interactions
- Author
-
Patrice V. Groomes, Usheer Kanjee, and Manoj T. Duraisingh
- Subjects
Infectious Diseases ,Erythrocytes ,Merozoites ,Plasmodium falciparum ,Protozoan Proteins ,Animals ,Humans ,Parasitology ,Parasites ,Ligands ,Article ,Biomechanical Phenomena ,Malaria - Abstract
A critical step in malaria blood-stage infections is the invasion of red blood cells (RBCs) by merozoite forms of the Plasmodium parasite. Much progress has been made in defining the parasite ligands and host receptors that mediate this critical step. However, less well understood are the RBC biophysical determinants that influence parasite invasion. In this review we explore how Plasmodium falciparum merozoites interact with the RBC membrane during invasion to modulate RBC deformability and facilitate invasion. We further highlight RBC biomechanics-related polymorphisms that might have been selected for in human populations due to their ability to reduce parasite invasion. Such an understanding will reveal the translational potential of targeting host pathways affecting RBC biomechanical properties for the treatment of malaria.
- Published
- 2021
36. Pas-de-deux: African Plasmodium falciparum adaptations to sickle hemoglobin
- Author
-
Kai Matuschewski and Alexander Maier
- Subjects
Infectious Diseases ,Hemoglobin, Sickle ,Plasmodium falciparum ,Animals ,Humans ,Parasites ,Parasitology ,Anemia, Sickle Cell ,Malaria, Falciparum ,Malaria - Abstract
The molecular arms race between humans and Plasmodium falciparum in Africa resulted in selection of sickle-cell disease, which, on balance, protects heterozygote carriers against severe malaria. Band et al. discovered that parasites counter-adapt and can overcome disease resistance by identifying parasite genome signatures, termed P. falciparum sickle-associated (Pfsa) variants.
- Published
- 2022
37. Drug-induced hypersensitivity to artemisinin-based therapies for malaria
- Author
-
Michael Ramharter, Steffen Borrmann, and Tamara Nordmann
- Subjects
Allergy ,Combination therapy ,Plasmodium falciparum ,Antimalarials ,parasitic diseases ,medicine ,Hypersensitivity ,Humans ,Artemisinin ,Malaria, Falciparum ,biology ,business.industry ,medicine.disease ,biology.organism_classification ,Artemisinins ,Malaria ,Hypersensitivity reaction ,Infectious Diseases ,Tolerability ,Immunology ,Parasitology ,Drug Therapy, Combination ,business ,Adverse drug reaction ,medicine.drug - Abstract
In the early 2000s, artemisinin-based combination therapy (ACT) was introduced as first-line treatment for uncomplicated Plasmodium falciparum malaria in virtually all endemic countries. However, despite the well-known excellent tolerability of ACTs, hypersensitivity to artemisinin derivatives remains a repeatedly documented adverse drug reaction of still unknown frequency. The clinical features of an artemisinin-induced hypersensitivity reaction range from mild to life-threatening severity, and a significant number of cases may pass unnoticed. In this review, we discuss the medical importance of hypersensitivity to artemisinin derivatives and we review data on the presumed frequency and its potential underlying mechanisms. Furthermore, we advocate to make alternative non-artemisinin-based drugs available for patients who do not tolerate artemisinin derivatives and to continue investing in the development of novel non-artemisinin-based combination regimens.
- Published
- 2021
38. Targeting Pregnant Women for Malaria Surveillance
- Author
-
Patrick G T Walker, Alfredo Mayor, and Clara Menéndez
- Subjects
0301 basic medicine ,Plasmodium falciparum ,030231 tropical medicine ,Population ,Article ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Environmental health ,Intervention (counseling) ,parasitic diseases ,Humans ,Medicine ,Malaria surveillance ,education ,Africa South of the Sahara ,education.field_of_study ,Community level ,biology ,business.industry ,Prenatal Care ,medicine.disease ,biology.organism_classification ,Malaria ,030104 developmental biology ,Infectious Diseases ,Infectious disease (medical specialty) ,Population Surveillance ,Female ,Parasitology ,business - Abstract
Women attending antenatal care (ANC) are a generally healthy, easy-access population, contributing valuable data for infectious disease surveillance at the community level. ANC-based malaria surveillance would provide a routine measure of the malaria burden in pregnancy, which countries lack, whilst potentially improving pregnancy outcomes. It could also offer contemporary information on temporal trends and the geographic distribution of malaria burden as well as intervention coverage in the population to guide resource allocation and to assess progress towards elimination. Here, we review the factors underlying the relationship between Plasmodium falciparum in pregnancy and in the community, and outline strengths and limitations of an ANC-based surveillance in sub-Saharan Africa, its potential role within wider malaria surveillance systems, and subsequent programmatic applications.
- Published
- 2019
39. Molecular surveillance of malaria scales up
- Author
-
Daniel E. Neafsey and Philipp Schwabl
- Subjects
Genetic diversity ,Plasmodium falciparum ,Drug Resistance ,Computational biology ,Drug resistance ,Biology ,medicine.disease ,Genome ,Malaria ,Infectious Diseases ,Vector (epidemiology) ,Amplicon sequencing ,medicine ,Humans ,Parasitology ,Malaria, Falciparum ,Malaria control ,Genotyping - Abstract
Parasite and vector genetic data can guide malaria control, and technological advances are enabling more informative genetic data generation at unprecedented scales. Jacob et al. employ multiplexed amplicon sequencing to profile parasite genetic diversity from thousands of malaria samples, illuminating spatiotemporal patterns of drug resistance to inform regional drug policy change.
- Published
- 2021
40. Complex infections in vivax malaria: the more you look, the more you find
- Author
-
Alyssa E. Barry
- Subjects
Whole genome sequencing ,biology ,Plasmodium falciparum ,Plasmodium vivax ,medicine.disease ,biology.organism_classification ,Virology ,Article ,Infectious Diseases ,Single cell sequencing ,parasitic diseases ,Vivax malaria ,Malaria, Vivax ,medicine ,Humans ,Parasite hosting ,Parasitology ,Malaria, Falciparum ,Genotyping ,Malaria - Abstract
Population genomics of bulk malaria infections is unable to examine intrahost evolution, so most work has focused on the role of recombination in generating genetic variation. We used single cell sequencing protocol for low parasitemia infections to generate 406 near complete single Plasmodium vivax genomes from 11 patients sampled during sequential febrile episodes. Parasite genomes contained hundreds of de novo mutations, showing strong signatures of selection, which are enriched in the ApiAP2 family of transcription factors, known targets of adaptation. Comparing 315 P. falciparum single cell genomes from 15 patients with our P. vivax data we find broad complementary patterns of de novo mutation at the gene and pathway level, revealing the importance of within host evolution during malaria infections.
- Published
- 2021
41. Assessing risks of Plasmodium falciparum resistance to select next-generation antimalarials
- Author
-
David A. Fidock, Timothy N. C. Wells, Didier Leroy, Jeremy N. Burrows, Benjamin Blasco, and Maëlle Duffey
- Subjects
0301 basic medicine ,Drug ,medicine.medical_specialty ,media_common.quotation_subject ,030231 tropical medicine ,Plasmodium falciparum ,Drug Resistance ,Drug resistance ,Risk Assessment ,Article ,03 medical and health sciences ,Antimalarials ,0302 clinical medicine ,Medicine ,Malaria, Falciparum ,Intensive care medicine ,media_common ,Resistance (ecology) ,biology ,business.industry ,Drug discovery ,biology.organism_classification ,medicine.disease ,Resistome ,030104 developmental biology ,Infectious Diseases ,Drug development ,Parasitology ,business ,Malaria - Abstract
Strategies to counteract or prevent emerging drug resistance are crucial for the design of next-generation antimalarials. In the past, resistant parasites were generally identified following treatment failures in patients, and compounds would have to be abandoned late in development. An early understanding of how candidate therapeutics lose efficacy as parasites evolve resistance is important to facilitate drug design and improve resistance detection and monitoring up to the postregistration phase. We describe a new strategy to assess resistance to antimalarial compounds as early as possible in preclinical development by leveraging tools to define the Plasmodium falciparum resistome, predict potential resistance risks of clinical failure for candidate therapeutics, and inform decisions to guide antimalarial drug development.
- Published
- 2021
42. Anopheles stephensi (Asian Malaria Mosquito)
- Author
-
Sampath Kumar, Farah Ishtiaq, and Sunita Swain
- Subjects
Mosquito Control ,Traditional medicine ,Plasmodium falciparum ,Mosquito Vectors ,Biology ,medicine.disease ,biology.organism_classification ,Malaria ,Infectious Diseases ,Anopheles ,medicine ,Animals ,Parasitology ,Plasmodium vivax ,Animal Distribution ,Anopheles stephensi ,Asia, Southeastern - Published
- 2021
43. VAR2CSA Antibodies in Non-Pregnant Populations
- Author
-
Stephanie K. Yanow and Sedami Gnidehou
- Subjects
0301 basic medicine ,030231 tropical medicine ,Antibodies, Protozoan ,Antigens, Protozoan ,Serology ,03 medical and health sciences ,0302 clinical medicine ,parasitic diseases ,medicine ,Humans ,Malaria, Falciparum ,Pregnancy ,biology ,business.industry ,Research ,Plasmodium falciparum ,biology.organism_classification ,medicine.disease ,Non pregnant ,030104 developmental biology ,Infectious Diseases ,Immunoglobulin G ,embryonic structures ,Immunology ,biology.protein ,Parasitology ,Antibody ,business ,Malaria - Abstract
The Plasmodium falciparum protein VAR2CSA is a critical mediator of placental malaria, and VAR2CSA antibodies (IgGs) are important to protect pregnant women. Although infrequently detected outside pregnancy, VAR2CSA IgGs were reported in men and children from Colombia and Brazil and in select African populations. These findings raise questions about the specificity of VAR2CSA IgGs and the mechanisms by which they are acquired outside pregnancy. Here we review the data on VAR2CSA IgGs in men and children from different malaria-endemic regions. We discuss experimental factors that may affect interpretation of the serological data and consider the biological relevance of VAR2CSA IgGs in non-pregnant populations. We propose potential mechanisms for the acquisition of VARCSA IgGs outside of pregnancy. We identify knowledge gaps and research priorities.
- Published
- 2020
44. Why Asymptomatic Plasmodium falciparum Infections Are Common in Low-Transmission Settings
- Author
-
Ulrika Morris and Anders Björkman
- Subjects
0301 basic medicine ,Host immunity ,030231 tropical medicine ,Plasmodium falciparum ,Virulence ,Low transmission ,Asymptomatic ,Herd immunity ,03 medical and health sciences ,0302 clinical medicine ,Immunity ,parasitic diseases ,medicine ,Prevalence ,Animals ,Humans ,Malaria, Falciparum ,Selection, Genetic ,Asymptomatic Infections ,biology ,Host (biology) ,biology.organism_classification ,030104 developmental biology ,Infectious Diseases ,Immunology ,Parasitology ,medicine.symptom - Abstract
Plasmodium falciparum infections in low-transmission settings are often asymptomatic with low parasite densities despite low herd immunity. Based on studies in Zanzibar, this may be due to parasitic (nonvirulence) rather than host (immunity) factors. In high-transmission settings, high replication rate and virulence represents a competitive advantage, whereas in low-transmission settings nonvirulent parasites escape both competition and treatment. Such parasites also survive longer in low-transmission settings due to lower host immunity response and less frequent indirect drug exposure. This has major implications for optimal malaria control and elimination strategies.
- Published
- 2020
45. Precipitated Malaria: It Never Rains but It Pours
- Author
-
Lars Hviid
- Subjects
0301 basic medicine ,030231 tropical medicine ,Plasmodium falciparum ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Immunity ,parasitic diseases ,medicine ,Humans ,Splenic Diseases ,Pregnancy ,biology ,business.industry ,medicine.disease ,biology.organism_classification ,Acquired immune system ,Malaria ,030104 developmental biology ,Infectious Diseases ,Immunology ,Wounds and Injuries ,Parasitology ,business ,Spleen - Abstract
Occasionally, Plasmodium falciparum malaria is apparently precipitated by traumatic events (e.g., a landmine accident) or by noninfectious events (e.g., pregnancy). The authors reporting such cases often seem as baffled as many of their readers probably are. However, the case reports may contain important clues regarding malaria pathogenesis and immunity.
- Published
- 2020
46. Endocytosis in Plasmodium and Toxoplasma Parasites
- Author
-
Ricarda Sabitzki, Tobias Spielmann, Markus Meissner, and Simon Gras
- Subjects
0301 basic medicine ,Plasmodium ,030231 tropical medicine ,Endocytic cycle ,Drug Resistance ,Endocytosis ,03 medical and health sciences ,0302 clinical medicine ,parasitic diseases ,Extracellular ,Animals ,Humans ,Host cell cytosol ,biology ,Antiparasitic Agents ,Toxoplasma gondii ,Plasmodium falciparum ,biology.organism_classification ,Artemisinins ,Cell biology ,030104 developmental biology ,Infectious Diseases ,Parasitology ,Toxoplasma ,Intracellular - Abstract
Endocytosis is critical for many functions in eukaryotic cells. Uptake of host cell cytosol, an indispensable endocytic process in malaria blood-stage parasites, has been known for a long time. However, it is only recently that the proteins involved in this process have started to emerge. Unexpectedly, some of these proteins revealed a critical role for endocytosis in artemisinin resistance. More recently, endocytosis was discovered in both intracellular and extracellular Toxoplasma gondii parasites. Here, we review these findings, compare the endolysosomal systems of Toxoplasma and Plasmodium parasites, and present current knowledge about endocytic mechanisms in apicomplexans.
- Published
- 2020
47. The Human Spleen in Malaria: Filter or Shelter?
- Author
-
Benoît Henry, Camille Roussel, Mario Carucci, Valentine Brousse, Papa Alioune Ndour, Pierre Buffet, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP)
- Subjects
0301 basic medicine ,Erythrocytes ,Anemia ,[SDV]Life Sciences [q-bio] ,030231 tropical medicine ,Plasmodium falciparum ,Spleen ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,parasitic diseases ,Gametocyte ,Medicine ,Humans ,Malaria, Falciparum ,business.industry ,medicine.disease ,Acquired immune system ,Hemolysis ,3. Good health ,Red blood cell ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,Immunology ,Parasitology ,business ,Malaria - Abstract
The human spleen is an immune sentinel and controls red blood cell (RBC) quality. By mechanically retaining subsets of infected RBCs, the spleen may reduce the pace at which the parasite biomass increases before the adaptive immune response operates. Conversely, the spleen may contribute to malaria pathogenesis, particularly anemia that is associated with splenomegaly. Large spleens may also shelter parasites in chronic carriers. Upon treatment with artemisinins, the spleen clears circulating parasites by pitting and releases 'once-infected' RBCs in circulation. This triggers postartesunate delayed hemolysis and explains the long post-treatment positivity of histidine-rich protein 2 (HRP2)-based dipsticks. Importantly, splenic retention of RBCs also applies to gametocytes, the clearance of which may be enhanced by stiffening them with drugs, a potential way to block malaria transmission.
- Published
- 2019
48. Malaria in Italy – Migrants Are Not the Cause
- Author
-
Giovanni Benelli, Marco Pombi, and Domenico Otranto
- Subjects
invasive mosquitoes ,Plasmodium falciparum ,030231 tropical medicine ,Anopheles labranchiae ,Anopheles sacharovi ,Anopheles superpictus ,travel medicine ,Humans ,Italy ,Malaria ,Risk Factors ,Transients and Migrants ,03 medical and health sciences ,Politics ,0302 clinical medicine ,anopheles labranchiae ,anopheles sacharovi ,anopheles superpictus ,plasmodium falciparum ,parasitology ,infectious diseases ,parasitic diseases ,medicine ,030212 general & internal medicine ,Socioeconomics ,medicine.disease ,Infectious Diseases ,Geography ,Parasitology ,human activities - Abstract
Recently, five cases of malaria were reported in Italy. These people had not travelled abroad, prompting some media and political organizations to fuel a climate of fear by connecting the cases with migrants coming into the country. Here, we discuss scientific data highlighting the limited risk of malaria reintroduction in Italy.
- Published
- 2018
49. Evolutionary ARMS Race: Antimalarial Resistance Molecular Surveillance
- Author
-
Rogan Lee, John Ellis, Wieland Meyer, and Christiane Prosser
- Subjects
0301 basic medicine ,Plasmodium ,Drug Resistance ,Mycology & Parasitology ,Drug resistance ,Antimalarials ,03 medical and health sciences ,Evolutionary arms race ,Environmental health ,parasitic diseases ,medicine ,Humans ,Artemisinin ,mHealth ,Disease burden ,biology ,Plasmodium falciparum ,biology.organism_classification ,medicine.disease ,Drug Resistance, Multiple ,Malaria ,Multiple drug resistance ,030104 developmental biology ,Infectious Diseases ,Population Surveillance ,Parasitology ,Business ,medicine.drug - Abstract
© 2018 Elsevier Ltd Molecular surveillance of antimalarial drug resistance markers has become an important part of resistance detection and containment. In the current climate of multidrug resistance, including resistance to the global front-line drug artemisinin, there is a consensus to upscale molecular surveillance. The most salient limitation to current surveillance efforts is that skill and infrastructure requirements preclude many regions. This includes sub-Saharan Africa, where Plasmodium falciparum is responsible for most of the global malaria disease burden. New molecular and data technologies have emerged with an emphasis on accessibility. These may allow surveillance to be conducted in broad settings where it is most needed, including at the primary healthcare level in endemic countries, and extending to the village health worker.
- Published
- 2018
50. Advancing Research Models and Technologies to Overcome Biological Barriers to Plasmodium vivax Control
- Author
-
Jennifer S. Armistead and John H. Adams
- Subjects
0301 basic medicine ,biology ,Transmission (medicine) ,Research ,030231 tropical medicine ,Plasmodium vivax ,Plasmodium falciparum ,biology.organism_classification ,medicine.disease ,Article ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Infectious Diseases ,Environmental health ,parasitic diseases ,Vivax malaria ,Immunology ,Malaria, Vivax ,medicine ,Humans ,Parasitology ,Malaria - Abstract
Malaria prevalence has declined in the past 10 years, especially outside of sub-Saharan Africa. However, the proportion of cases due to Plasmodium vivax is increasing, accounting for up to 90-100% of the malaria burden in endemic regions. Nonetheless, investments in malaria research and control still prioritize Plasmodium falciparum while largely neglecting P. vivax. Specific biological features of P. vivax, particularly invasion of reticulocytes, occurrence of dormant liver forms of the parasite, and the potential for transmission of sexual-stage parasites prior to onset of clinical illness, promote its persistence and hinder development of research tools and interventions. This review discusses recent advances in P. vivax research, current knowledge of its unique biology, and proposes priorities for P. vivax research and control efforts.
- Published
- 2018
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