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Virulence Dec 2023Infections with and cause over 600,000 deaths each year, concentrated in Africa and in young children, but much of the world's population remain at risk of infection.... (Review)
Review
Infections with and cause over 600,000 deaths each year, concentrated in Africa and in young children, but much of the world's population remain at risk of infection. In this article, we review the latest developments in the immunogenicity and pathogenesis of malaria, with a particular focus on , the leading malaria killer. Pathogenic factors include parasite-derived toxins and variant surface antigens on infected erythrocytes that mediate sequestration in the deep vasculature. Host response to parasite toxins and to variant antigens is an important determinant of disease severity. Understanding how parasites sequester, and how antibody to variant antigens could prevent sequestration, may lead to new approaches to treat and prevent disease. Difficulties in malaria diagnosis, drug resistance, and specific challenges of treating pose challenges to malaria elimination, but vaccines and other preventive strategies may offer improved disease control.
Topics: Child; Humans; Child, Preschool; Virulence; Malaria; Malaria, Falciparum; Plasmodium falciparum; Plasmodium vivax; Protozoan Proteins
PubMed: 36419237
DOI: 10.1080/21505594.2022.2150456 -
Clinical Microbiology Reviews Sep 2019Protozoan parasites are the causative agents of malaria, a deadly disease that continues to afflict hundreds of millions of people every year. Infections with malaria... (Review)
Review
Protozoan parasites are the causative agents of malaria, a deadly disease that continues to afflict hundreds of millions of people every year. Infections with malaria parasites can be asymptomatic, with mild or severe symptoms, or fatal, depending on many factors such as parasite virulence and host immune status. Malaria can be treated with various drugs, with artemisinin-based combination therapies (ACTs) being the first-line choice. Recent advances in genetics and genomics of malaria parasites have contributed greatly to our understanding of parasite population dynamics, transmission, drug responses, and pathogenesis. However, knowledge gaps in parasite biology and host-parasite interactions still remain. Parasites resistant to multiple antimalarial drugs have emerged, while advanced clinical trials have shown partial efficacy for one available vaccine. Here we discuss genetic and genomic studies of biology, host-parasite interactions, population structures, mosquito infectivity, antigenic variation, and targets for treatment and immunization. Knowledge from these studies will advance our understanding of malaria pathogenesis, epidemiology, and evolution and will support work to discover and develop new medicines and vaccines.
Topics: Antimalarials; Drug Resistance; Evolution, Molecular; Genome, Protozoan; Humans; Malaria; Plasmodium
PubMed: 31366610
DOI: 10.1128/CMR.00019-19 -
Microbiology Spectrum Jul 2019Malaria is a vector-borne disease that involves multiple parasite species in a variety of ecological settings. However, the parasite species causing the disease, the... (Review)
Review
Malaria is a vector-borne disease that involves multiple parasite species in a variety of ecological settings. However, the parasite species causing the disease, the prevalence of subclinical infections, the emergence of drug resistance, the scale-up of interventions, and the ecological factors affecting malaria transmission, among others, are aspects that vary across areas where malaria is endemic. Such complexities have propelled the study of parasite genetic diversity patterns in the context of epidemiologic investigations. Importantly, molecular studies indicate that the time and spatial distribution of malaria cases reflect epidemiologic processes that cannot be fully understood without characterizing the evolutionary forces shaping parasite population genetic patterns. Although broad in scope, this review in the Curated Collection: Advances in Molecular Epidemiology highlights the need for understanding population genetic concepts when interpreting parasite molecular data. First, we discuss malaria complexity in terms of the parasite species involved. Second, we describe how molecular data are changing our understanding of malaria incidence and infectiousness. Third, we compare different approaches to generate parasite genetic information in the context of epidemiologically relevant questions related to malaria control. Finally, we describe a few genomic studies as evidence of how these approaches will provide new insights into the malaria disease dynamics. *This article is part of a curated collection.
Topics: Animals; Evolution, Molecular; Genome, Protozoan; Humans; Malaria; Molecular Epidemiology; Plasmodium
PubMed: 31400095
DOI: 10.1128/microbiolspec.AME-0010-2019 -
Trends in Parasitology Oct 2023Meiosis is sexual cell division, a process in eukaryotes whereby haploid gametes are produced. Compared to canonical model eukaryotes, meiosis in apicomplexan parasites... (Review)
Review
Meiosis is sexual cell division, a process in eukaryotes whereby haploid gametes are produced. Compared to canonical model eukaryotes, meiosis in apicomplexan parasites appears to diverge from the process with respect to the molecular mechanisms involved; the biology of Plasmodium meiosis, and its regulation by means of post-translational modification, are largely unexplored. Here, we discuss the impact of technological advances in cell biology, evolutionary bioinformatics, and genome-wide functional studies on our understanding of meiosis in the Apicomplexa. These parasites, including Plasmodium falciparum, Toxoplasma gondii, and Eimeria spp., have significant socioeconomic impact on human and animal health. Understanding this key stage during the parasite's life cycle may well reveal attractive targets for therapeutic intervention.
Topics: Animals; Humans; Plasmodium; Eukaryota; Plasmodium falciparum; Meiosis; Toxoplasma
PubMed: 37541799
DOI: 10.1016/j.pt.2023.07.002 -
Proceedings of the National Academy of... Oct 2020Asymptomatic carriers of parasites hamper malaria control and eradication. Achieving malaria eradication requires ultrasensitive diagnostics for low parasite density...
Asymptomatic carriers of parasites hamper malaria control and eradication. Achieving malaria eradication requires ultrasensitive diagnostics for low parasite density infections (<100 parasites per microliter blood) that work in resource-limited settings (RLS). Sensitive point-of-care diagnostics are also lacking for nonfalciparum malaria, which is characterized by lower density infections and may require additional therapy for radical cure. Molecular methods, such as PCR, have high sensitivity and specificity, but remain high-complexity technologies impractical for RLS. Here we describe a CRISPR-based diagnostic for ultrasensitive detection and differentiation of , , , and , using the nucleic acid detection platform SHERLOCK (specific high-sensitivity enzymatic reporter unlocking). We present a streamlined, field-applicable, diagnostic comprised of a 10-min SHERLOCK parasite rapid extraction protocol, followed by SHERLOCK for 60 min for species-specific detection via fluorescent or lateral flow strip readout. We optimized one-pot, lyophilized, isothermal assays with a simplified sample preparation method independent of nucleic acid extraction, and showed that these assays are capable of detection below two parasites per microliter blood, a limit of detection suggested by the World Health Organization. Our and assays exhibited 100% sensitivity and specificity on clinical samples (5 and 10 samples). This work establishes a field-applicable diagnostic for ultrasensitive detection of asymptomatic carriers as well as a rapid point-of-care clinical diagnostic for nonfalciparum malaria species and low parasite density infections.
Topics: Carrier State; Clustered Regularly Interspaced Short Palindromic Repeats; Diagnostic Techniques and Procedures; Genetic Techniques; Humans; Malaria; Plasmodium
PubMed: 32958655
DOI: 10.1073/pnas.2010196117 -
Briefings in Functional Genomics Sep 2019
Topics: Chromatin; Gene Expression Regulation; Genomics; Plasmodium
PubMed: 31696202
DOI: 10.1093/bfgp/elz020 -
Genes May 2021Genomics has revolutionised the study of the biology of parasitic diseases. The first Eukaryotic parasite to have its genome sequenced was the malaria parasite . Since... (Review)
Review
Genomics has revolutionised the study of the biology of parasitic diseases. The first Eukaryotic parasite to have its genome sequenced was the malaria parasite . Since then, genomics has continued to lead the way in the study of the genome biology of parasites, both in breadth-the number of species' genomes sequenced-and in depth-massive-scale genome re-sequencing of several key species. Here, we review some of the insights into the biology, evolution and population genetics of gained from genome sequencing, and look at potential new avenues in the future genome-scale study of its biology.
Topics: Epigenome; Genome, Protozoan; Humans; Malaria; Plasmodium falciparum; Polymorphism, Genetic
PubMed: 34070769
DOI: 10.3390/genes12060843 -
Cell Metabolism Mar 2024Severe forms of malaria are associated with systemic inflammation and host metabolism disorders; however, the interplay between these outcomes is poorly understood....
Severe forms of malaria are associated with systemic inflammation and host metabolism disorders; however, the interplay between these outcomes is poorly understood. Using a Plasmodium chabaudi model of malaria, we demonstrate that interferon (IFN) γ boosts glycolysis in splenic monocyte-derived dendritic cells (MODCs), leading to itaconate accumulation and disruption in the TCA cycle. Increased itaconate levels reduce mitochondrial functionality, which associates with organellar nucleic acid release and MODC restraint. We hypothesize that dysfunctional mitochondria release degraded DNA into the cytosol. Once mitochondrial DNA is sensitized, the activation of IRF3 and IRF7 promotes the expression of IFN-stimulated genes and checkpoint markers. Indeed, depletion of the STING-IRF3/IRF7 axis reduces PD-L1 expression, enabling activation of CD8+ T cells that control parasite proliferation. In summary, mitochondrial disruption caused by itaconate in MODCs leads to a suppressive effect in CD8+ T cells, which enhances parasitemia. We provide evidence that ACOD1 and itaconate are potential targets for adjunct antimalarial therapy.
Topics: Humans; Monocytes; DNA, Mitochondrial; B7-H1 Antigen; Plasmodium; Malaria; Mitochondria; Dendritic Cells; Succinates
PubMed: 38325373
DOI: 10.1016/j.cmet.2024.01.008 -
Parasites & Vectors Apr 2023Malaria is a vector-borne parasitic disease caused by the apicomplexan protozoan parasite Plasmodium. Malaria is a significant health problem and the leading cause of... (Review)
Review
Malaria is a vector-borne parasitic disease caused by the apicomplexan protozoan parasite Plasmodium. Malaria is a significant health problem and the leading cause of socioeconomic losses in developing countries. WHO approved several antimalarials in the last 2 decades, but the growing resistance against the available drugs has worsened the scenario. Drug resistance and diversity among Plasmodium strains hinder the path of eradicating malaria leading to the use of new technologies and strategies to develop effective vaccines and drugs. A timely and accurate diagnosis is crucial for any disease, including malaria. The available diagnostic methods for malaria include microscopy, RDT, PCR, and non-invasive diagnosis. Recently, there have been several developments in detecting malaria, with improvements leading to achieving an accurate, quick, cost-effective, and non-invasive diagnostic tool for malaria. Several vaccine candidates with new methods and antigens are under investigation and moving forward to be considered for clinical trials. This article concisely reviews basic malaria biology, the parasite's life cycle, approved drugs, vaccine candidates, and available diagnostic approaches. It emphasizes new avenues of therapeutics for malaria.
Topics: Humans; Malaria Vaccines; Malaria; Plasmodium; Antimalarials; Antigens, Protozoan; Malaria, Falciparum; Plasmodium falciparum
PubMed: 37060004
DOI: 10.1186/s13071-023-05755-8 -
Trends in Parasitology Jul 2022Plasmodium parasites extensively alter their host hepatocyte to evade host detection and support an unprecedented replication rate. Host cell manipulation includes... (Review)
Review
Plasmodium parasites extensively alter their host hepatocyte to evade host detection and support an unprecedented replication rate. Host cell manipulation includes association with the host early and late endomembrane systems, where Plasmodium accesses nutrients while suppressing cellular immune processes. Early endomembrane organelles provide an opportunity to sequester an abundance of lipids and proteins, but the association with late endomembrane organelles also risks autophagy-mediated elimination. While not all parasites survive, those that do benefit from a plethora of nutrients provided through this pathway. In this review, we discuss recent advances in our understanding of how Plasmodium parasites balance the need for host nutrients while avoiding elimination during the liver stage.
Topics: Animals; Hepatocytes; Liver; Nutrients; Parasites; Plasmodium
PubMed: 35534377
DOI: 10.1016/j.pt.2022.04.004