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Cold Spring Harbor Perspectives in... Jan 2018In the mosquito-human life cycle, the six species of malaria parasites infecting humans (, , , , , and ) undergo 10 or more morphological states, replicate from single... (Review)
Review
In the mosquito-human life cycle, the six species of malaria parasites infecting humans (, , , , , and ) undergo 10 or more morphological states, replicate from single to 10,000+ cells, and vary in total population from one to many more than 10 organisms. In the human host, only a small number of these morphological stages lead to clinical disease and the vast majority of all malaria-infected patients in the world produce few (if any) symptoms in the human. Human clinical disease (e.g., fever, anemia, coma) is the result of the parasite preprogrammed biology in concert with the human pathophysiological response. Caveats and corollaries that add variation to this host-parasite interaction include parasite genetic diversity of key proteins, coinfections, comorbidities, delays in treatment, human polymorphisms, and environmental determinants.
Topics: Female; Humans; Malaria; Malaria, Cerebral; Placenta; Plasmodium; Pregnancy; Species Specificity; Virulence Factors
PubMed: 28533315
DOI: 10.1101/cshperspect.a025569 -
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 -
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 -
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 -
Frontiers in Cellular and Infection... 2021Malaria is a highly inflammatory and oxidative disease. The production of reactive oxygen species by host phagocytes is an essential component of the host response to... (Review)
Review
Malaria is a highly inflammatory and oxidative disease. The production of reactive oxygen species by host phagocytes is an essential component of the host response to infection. Moreover, host oxidative enzymes, such as xanthine oxidase, are upregulated in malaria patients. Although increased production of reactive oxygen species contributes to the clearance of the parasite, excessive amounts of these free radicals can mediate inflammation and cause extensive damage to host cells and tissues, probably contributing to severe pathologies. has a variety of antioxidant enzymes that allow it to survive amidst this oxidative onslaught. However, parasitic degradation of hemoglobin within the infected red blood cell generates free heme, which is released at the end of the replication cycle, further aggravating the oxidative burden on the host and possibly contributing to the severity of life-threatening malarial complications. Additionally, the highly inflammatory response to malaria contributes to exacerbate the oxidative response. In this review, we discuss host and parasite-derived sources of oxidative stress that may promote severe disease in infection. Therapeutics that restore and maintain oxidative balance in malaria patients may be useful in preventing lethal complications of this disease.
Topics: Erythrocytes; Humans; Malaria; Malaria, Falciparum; Oxidative Stress; Plasmodium; Plasmodium falciparum
PubMed: 34917519
DOI: 10.3389/fcimb.2021.768182 -
Malaria Journal May 2018Malaria parasites (genus Plasmodium) are widespread in birds. These pathogens cause pathology of blood and various organs, often resulting in severe avian malaria.... (Review)
Review
BACKGROUND
Malaria parasites (genus Plasmodium) are widespread in birds. These pathogens cause pathology of blood and various organs, often resulting in severe avian malaria. Numerous recent studies have reported DNA sequences of avian malaria parasites, indicating rich genetic diversity and the possible existence of many undescribed species. However, the majority of reported Plasmodium lineages remain unidentified to species level, and molecular characterization is unavailable for the majority of described Plasmodium parasites. During the past 15 years, numerous new Plasmodium species have been described. However, keys for their identification are unavailable or incomplete. Identification of avian malaria parasites remains a difficult task even for experts, and this precludes development of avian malariology, particularly in wildlife. Here, keys for avian malaria parasites have been developed as a baseline for assisting academic and veterinary medicine researchers in identification of these pathogens. The main obstacles and future research priorities have been defined in the taxonomy of avian Plasmodium species.
METHODS
The data were considered from published articles and type and voucher material, which was accessed in museums in Europe, the USA and Australia. Blood films containing various blood stages of the majority of described species were examined and used for the development of dichotomous keys for avian Plasmodium species.
RESULTS
In all, 164 published articles were included in this review. Blood stages of avian Plasmodium parasites belonging to subgenera Haemamoeba, Giovannolaia, Novyella, Bennettinia and Huffia were analysed and compared. Illustrated keys for identification of subgenera and species of these parasites were developed. Lists of invalid and synonymous Plasmodium parasite names as well as names of doubtful identity were composed.
CONCLUSION
This study shows that 55 described species of avian Plasmodium can be readily identified using morphological features of their blood stages. These were incorporated in the keys. Numerous synonymous names of Plasmodium species and also the names belonging to the category species inquirenda exist, and they can be used as reserves for future taxonomy studies. Molecular markers are unavailable for 58% of described Plasmodium parasites, raising a task for the current avian malaria researchers to fill up this gap.
Topics: Animals; Malaria, Avian; Plasmodium
PubMed: 29843718
DOI: 10.1186/s12936-018-2359-5 -
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