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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 -
The American Journal of Tropical... Jul 2018Important strides have been made within the past decade toward malaria elimination in many regions, and with this progress, the feasibility of eradication is once again... (Review)
Review
Important strides have been made within the past decade toward malaria elimination in many regions, and with this progress, the feasibility of eradication is once again under discussion. If the ambitious goal of eradication is to be achieved by 2040, all species of infecting humans will need to be targeted with evidence-based and concerted interventions. In this perspective, the potential barriers to achieving global malaria elimination are discussed with respect to the related diversities in host, parasite, and vector populations. We argue that control strategies need to be reorientated from a sequential attack on each species, dominated by to one that targets all species in parallel. A set of research themes is proposed to mitigate the potential setbacks on the pathway to a malaria-free world.
Topics: Animals; Anopheles; Antimalarials; Chloroquine; Disease Eradication; Host-Parasite Interactions; Humans; Malaria; Malaria, Falciparum; Malaria, Vivax; Mosquito Vectors; Plasmodium falciparum; Plasmodium knowlesi; Plasmodium malariae; Plasmodium ovale; Plasmodium vivax; Primaquine
PubMed: 29761762
DOI: 10.4269/ajtmh.17-0869 -
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 -
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 -
Current Opinion in Microbiology Dec 2020Malaria continues to pose a severe threat to over half of the world's population each year. With no long-term, effective vaccine available and a growing resistance to... (Review)
Review
Malaria continues to pose a severe threat to over half of the world's population each year. With no long-term, effective vaccine available and a growing resistance to antimalarials, there is a need for innovative methods of Plasmodium treatment. Recent evidence has pointed to a role of the composition of the gut microbiota in the severity of Plasmodium infection in both animal models and human studies. Further evidence has shown that the gut microbiota influences the adaptive immune response of the host, the arm of the immune system necessary for Plasmodium clearance, sustained Plasmodium immunity, and vaccine efficacy. Together, this illustrates the future potential of gut microbiota modulation as a novel method of preventing severe malaria.
Topics: Adaptive Immunity; Animals; Bacteria; Gastrointestinal Microbiome; Humans; Immunity; Malaria; Malaria Vaccines; Plasmodium
PubMed: 33007644
DOI: 10.1016/j.mib.2020.08.006 -
Malaria Journal May 2022The global malaria burden sometimes obscures that the genus Plasmodium comprises diverse clades with lineages that independently gave origin to the extant human... (Review)
Review
The global malaria burden sometimes obscures that the genus Plasmodium comprises diverse clades with lineages that independently gave origin to the extant human parasites. Indeed, the differences between the human malaria parasites were highlighted in the classical taxonomy by dividing them into two subgenera, the subgenus Plasmodium, which included all the human parasites but Plasmodium falciparum that was placed in its separate subgenus, Laverania. Here, the evolution of Plasmodium in primates will be discussed in terms of their species diversity and some of their distinct phenotypes, putative molecular adaptations, and host-parasite biocenosis. Thus, in addition to a current phylogeny using genome-level data, some specific molecular features will be discussed as examples of how these parasites have diverged. The two subgenera of malaria parasites found in primates, Plasmodium and Laverania, reflect extant monophyletic groups that originated in Africa. However, the subgenus Plasmodium involves species in Southeast Asia that were likely the result of adaptive radiation. Such events led to the Plasmodium vivax lineage. Although the Laverania species, including P. falciparum, has been considered to share "avian characteristics," molecular traits that were likely in the common ancestor of primate and avian parasites are sometimes kept in the Plasmodium subgenus while being lost in Laverania. Assessing how molecular traits in the primate malaria clades originated is a fundamental science problem that will likely provide new targets for interventions. However, given that the genus Plasmodium is paraphyletic (some descendant groups are in other genera), understanding the evolution of malaria parasites will benefit from studying "non-Plasmodium" Haemosporida.
Topics: Animals; Malaria; Malaria, Falciparum; Plasmodium; Plasmodium falciparum; Plasmodium vivax
PubMed: 35505356
DOI: 10.1186/s12936-022-04130-9 -
International Journal For Parasitology Feb 2017Parasites such as Plasmodium and Toxoplasma possess a vestigial plastid homologous to the chloroplasts of algae and plants. The plastid (known as the apicoplast; for... (Review)
Review
Parasites such as Plasmodium and Toxoplasma possess a vestigial plastid homologous to the chloroplasts of algae and plants. The plastid (known as the apicoplast; for apicomplexan plastid) is non-photosynthetic and very much reduced, but has clear endosymbiotic ancestry including a circular genome that encodes RNAs and proteins and a suite of bacterial biosynthetic pathways. Here we review the initial discovery of the apicoplast, and recount the major new insights into apicoplast origin, biogenesis and function. We conclude by examining how the apicoplast can be removed from malaria parasites in vitro, ultimately completing its reduction by chemical supplementation.
Topics: Animals; Apicoplasts; Biological Evolution; Humans; Plasmodium; Symbiosis
PubMed: 27773518
DOI: 10.1016/j.ijpara.2016.08.005 -
Malaria Journal May 2022Malaria is a vector-borne disease caused by protozoan parasites of the genus Plasmodium. Plasmodium vivax is the most prevalent human-infecting species in the Americas.... (Review)
Review
Malaria is a vector-borne disease caused by protozoan parasites of the genus Plasmodium. Plasmodium vivax is the most prevalent human-infecting species in the Americas. However, the origins of this parasite in this continent are still debated. Similarly, it is now accepted that the existence of Plasmodium simium is explained by a P. vivax transfer from humans to monkey in America. However, many uncertainties still exist concerning the origin of the transfer and whether several transfers occurred. In this review, the most recent studies that addressed these questions using genetic and genomic approaches are presented.
Topics: Biological Evolution; Genome; Humans; Malaria; Plasmodium; Plasmodium vivax
PubMed: 35505431
DOI: 10.1186/s12936-022-04132-7 -
Proceedings of the National Academy of... Mar 20225-methylcytosine (mC) is an important epitranscriptomic modification involved in messenger RNA (mRNA) stability and translation efficiency in various biological...
5-methylcytosine (mC) is an important epitranscriptomic modification involved in messenger RNA (mRNA) stability and translation efficiency in various biological processes. However, it remains unclear if mC modification contributes to the dynamic regulation of the transcriptome during the developmental cycles of parasites. Here, we characterize the landscape of mC mRNA modifications at single nucleotide resolution in the asexual replication stages and gametocyte sexual stages of rodent () and human () malaria parasites. While different representations of mC-modified mRNAs are associated with the different stages, the abundance of the mC marker is strikingly enhanced in the transcriptomes of gametocytes. Our results show that mC modifications confer stability to the transcripts and that a ortholog of NSUN2 is a major mRNA mC methyltransferase in malaria parasites. Upon knockout of (), marked reductions of mC modification were observed in a panel of gametocytogenesis-associated transcripts. These reductions correlated with impaired gametocyte production in the knockout rodent malaria parasites. Restoration of the gene in the knockout parasites rescued the gametocyte production phenotype as well as mC modification of the gametocytogenesis-associated transcripts. Together with the mRNA mC profiles for two species of , our findings demonstrate a major role for NSUN2-mediated mC modifications in mRNA transcript stability and sexual differentiation in malaria parasites.
Topics: 5-Methylcytosine; Germ Cells; Plasmodium falciparum; Plasmodium yoelii; Protozoan Proteins; RNA, Messenger; Transcriptome
PubMed: 35210361
DOI: 10.1073/pnas.2110713119 -
Parasites & Vectors Mar 2018It is over 100 years since the life-cycle of the malaria parasite Plasmodium was discovered, yet its intricacies remain incompletely understood - a knowledge gap that... (Review)
Review
It is over 100 years since the life-cycle of the malaria parasite Plasmodium was discovered, yet its intricacies remain incompletely understood - a knowledge gap that may prove crucial for our efforts to control the disease. Phenotypic screens have partially filled the void in the antimalarial drug market, but as compound libraries eventually become exhausted, new medicines will only come from directed drug development based on a better understanding of fundamental parasite biology. This review focusses on the unusual cell cycles of Plasmodium, which may present a rich source of novel drug targets as well as a topic of fundamental biological interest. Plasmodium does not grow by conventional binary fission, but rather by several syncytial modes of replication including schizogony and sporogony. Here, we collate what is known about the various cell cycle events and their regulators throughout the Plasmodium life-cycle, highlighting the differences between Plasmodium, model organisms and other apicomplexan parasites and identifying areas where further study is required. The possibility of DNA replication and the cell cycle as a drug target is also explored. Finally the use of existing tools, emerging technologies, their limitations and future directions to elucidate the peculiarities of the Plasmodium cell cycle are discussed.
Topics: Cell Cycle; Cytological Techniques; DNA Replication; Drug Discovery; Parasitology; Plasmodium
PubMed: 29587837
DOI: 10.1186/s13071-018-2800-1