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Frontiers in Cellular and Infection... 2021The development of genetic manipulation of in the 1980s was key to study malaria biology. Genetically modified parasites have been used to study several aspects of the... (Review)
Review
The development of genetic manipulation of in the 1980s was key to study malaria biology. Genetically modified parasites have been used to study several aspects of the disease, such as red blood cell invasion, drug resistance mechanisms, gametocyte development and mosquito transmission. However, biological and genetic differences between and the other human malaria parasites make a poor model to study different species. The lack of robust systems of long-term culture of and the other human malaria parasites lagged the genetic manipulation of these species. Here we review the efforts to generate genetically modified non- human malaria parasites, and . Using models - infection of non-human primates such as rhesus macaques and saimiri monkeys - researchers were able to generate transgenic lines of , and . The development of long-term culture of in the 2000's, using rhesus and human red blood cells, created a platform to genetically manipulate non- malaria parasites. Recently, the use of CRISPR/Cas9 technology to genome edit provides another tool to non-falciparum malaria research, extending the possibilities and allowing researchers to study different aspects of the biology of these parasites and understand the differences between these species and .
Topics: Animals; Humans; Macaca mulatta; Malaria; Malaria, Vivax; Parasites; Plasmodium knowlesi; Plasmodium vivax
PubMed: 34527600
DOI: 10.3389/fcimb.2021.680460 -
Trends in Parasitology Apr 2021The phenomenon of relapsing malaria has been recognised for centuries. It is caused in humans by the parasite species Plasmodium vivax and Plasmodium ovale, which can... (Review)
Review
The phenomenon of relapsing malaria has been recognised for centuries. It is caused in humans by the parasite species Plasmodium vivax and Plasmodium ovale, which can arrest growth at an early, asymptomatic stage as hypnozoites inside liver cells. These dormant parasites can remain quiescent for months or years, then reactivate causing symptomatic malaria. The dynamics of hypnozoite dormancy and reactivation are well documented but the molecular basis remains a complete mystery. Here, I observe that the process has striking parallels with plant vernalisation, whereby plants remain dormant through the winter before flowering in spring. Vernalisation is thoroughly studied in several plant species and its mechanisms are known in exquisite detail. Vernalisation may thus provide a useful framework for interrogating hypnozoite biology.
Topics: Animals; Humans; Life Cycle Stages; Malaria; Plant Dormancy; Plasmodium ovale; Plasmodium vivax
PubMed: 33257270
DOI: 10.1016/j.pt.2020.11.001 -
Expert Review of Proteomics Aug 2016Plasmodium vivax has accounted for an enormous share of the global malaria burden in recent years, along with Plasmodium falciparum. The wide distribution of P. vivax... (Review)
Review
INTRODUCTION
Plasmodium vivax has accounted for an enormous share of the global malaria burden in recent years, along with Plasmodium falciparum. The wide distribution of P. vivax and recent evidences of severe and complicated vivax malaria across several endemic regions of the world suggest that this disease may have been more overlooked than benign. While P. falciparum has been extensively studied, P. vivax has received limited research attention owing to its complex nature and absence of a continuous culture system.
AREAS COVERED
This review briefly describes the epidemiology of vivax malaria, analyzes challenges towards effective control and summarizes major insights provided by genomics and transcriptomics research in the area. Subsequently, the review provides a detailed description of the applications of proteomics in vivax malaria research, focusing on both host responses and parasite proteomics studies to understand P. vivax biology. Expert commentary: In recent years, proteomics technologies are being used effectively to understand P. vivax biology and the underlying pathogenesis. Technological advances in mass spectrometry configurations, multiomics investigations and emerging strategies such as targeted proteomics may also immensely aid in studying disease severity, improving existing diagnosis and identifying new drug and vaccine targets.
Topics: Genomics; Humans; Malaria, Falciparum; Malaria, Vivax; Mass Spectrometry; Plasmodium falciparum; Plasmodium vivax; Proteome; Proteomics
PubMed: 27389635
DOI: 10.1080/14789450.2016.1210515 -
Annual Review of Microbiology Oct 2021is the most widespread human malaria parasite, in part because it can form latent liver stages known as hypnozoites after transmission by female anopheline mosquitoes... (Review)
Review
is the most widespread human malaria parasite, in part because it can form latent liver stages known as hypnozoites after transmission by female anopheline mosquitoes to human hosts. These persistent stages can activate weeks, months, or even years after the primary clinical infection; replicate; and initiate relapses of blood stage infection, which causes disease and recurring transmission. Eliminating hypnozoites is a substantial obstacle for malaria treatment and eradication since the hypnozoite reservoir is undetectable and unaffected by most antimalarial drugs. Importantly, in some parts of the globe where malaria is endemic, as many as 90% of blood stage infections are thought to be relapses rather than primary infections, rendering the hypnozoite a major driver of epidemiology. Here, we review the biology of the hypnozoite and recent discoveries concerning this enigmatic parasite stage. We discuss treatment and prevention challenges, novel animal models to study hypnozoites and relapse, and hypotheses related to hypnozoite formation and activation.
Topics: Animals; Female; Liver; Malaria; Malaria, Vivax; Plasmodium vivax; Recurrence
PubMed: 34196569
DOI: 10.1146/annurev-micro-032421-061155 -
European Journal of Immunology Aug 2023Regulatory and effector cell responses to Plasmodium vivax, the most common human malaria parasite outside Africa, remain understudied in naturally infected populations....
Regulatory and effector cell responses to Plasmodium vivax, the most common human malaria parasite outside Africa, remain understudied in naturally infected populations. Here, we describe peripheral CD4 T- and B-cell populations during and shortly after an uncomplicated P. vivax infection in 38 continuously exposed adult Amazonians. Consistent with previous observations, we found an increased frequency in CD4 CD45RA CD25 FoxP3 T regulatory cells that express the inhibitory molecule CTLA-4 during the acute infection, with a sustained expansion of CD21 CD27 atypical memory cells within the CD19 B-cell compartment. Both Th1- and Th2-type subsets of CXCR5 ICOS PD-1 circulating T follicular helper (cTfh) cells, which are thought to contribute to antibody production, were induced during P. vivax infection, with a positive correlation between overall cTfh cell frequency and IgG antibody titers to the P. vivax blood-stage antigen MSP1 . We identified significant changes in cell populations that had not been described in human malaria, such as an increased frequency of CTLA-4 T follicular regulatory cells that antagonize Tfh cells, and a decreased frequency of circulating CD24 CD27 B regulatory cells in response to acute infection. In conclusion, we disclose a complex immunoregulatory network that is critical to understand how naturally acquired immunity develops in P. vivax malaria.
Topics: Adult; Humans; Plasmodium vivax; CTLA-4 Antigen; Malaria, Vivax; T-Lymphocytes, Helper-Inducer; CD4-Positive T-Lymphocytes
PubMed: 37160134
DOI: 10.1002/eji.202350372 -
Parasitology International Apr 2022Plasmodium vivax is the most geographically widespread human malaria parasite. Global malaria efforts have been less successful at reducing the burden of P. vivax... (Review)
Review
Plasmodium vivax is the most geographically widespread human malaria parasite. Global malaria efforts have been less successful at reducing the burden of P. vivax compared to P. falciparum, owing to the unique biology and related treatment complexity of P. vivax. As a result, P. vivax is now the dominant malaria parasite throughout the Asia-Pacific and South America causing up to 14 million clinical cases every year and is considered a major obstacle to malaria elimination. Key features circumventing existing malaria control tools are the transmissibility of asymptomatic, low-density circulating infections and reservoirs of persistent dormant liver stages (hypnozoites) that are undetectable but reactivate to cause relapsing infections and sustain transmission. In this review we summarise the new knowledge shaping our understanding of the global epidemiology of P. vivax infections, highlighting the challenges for elimination and the tools that will be required achieve this.
Topics: Disease Reservoirs; Humans; Liver; Malaria, Falciparum; Malaria, Vivax; Plasmodium vivax
PubMed: 34896312
DOI: 10.1016/j.parint.2021.102526 -
Malaria Journal May 2021Loop-mediated isothermal amplification (LAMP) for malaria diagnosis at the point of care (POC) depends on the detection capacity of synthesized nucleic acids and the...
BACKGROUND
Loop-mediated isothermal amplification (LAMP) for malaria diagnosis at the point of care (POC) depends on the detection capacity of synthesized nucleic acids and the specificity of the amplification target. To improve malaria diagnosis, new colorimetric LAMP tests were developed using multicopy targets for Plasmodium vivax and Plasmodium falciparum detection.
METHODS
The cytochrome oxidase I (COX1) mitochondrial gene and the non-coding sequence Pvr47 for P. vivax, and the sub-telomeric sequence of erythrocyte membrane protein 1 (EMP1) and the non-coding sequence Pfr364 for P. falciparum were targeted to design new LAMP primers. The limit of detection (LOD) of each colorimetric LAMP was established and assessed with DNA extracted by mini spin column kit and the Boil & Spin method from 28 microscopy infections, 101 malaria submicroscopic infections detected by real-time PCR only, and 183 negatives infections by both microscopy and PCR.
RESULTS
The LODs for the colorimetric LAMPs were estimated between 2.4 to 3.7 parasites/µL of whole blood. For P. vivax detection, the colorimetric LAMP using the COX1 target showed a better performance than the Pvr47 target, whereas the Pfr364 target was the most specific for P. falciparum detection. All microscopic infections of P. vivax were detected by PvCOX1-LAMP using the mini spin column kit DNA extraction method and 81% (17/21) were detected using Boil & Spin sample preparation. Moreover, all microscopic infections of P. falciparum were detected by Pfr364-LAMP using both sample preparation methods. In total, PvCOX1-LAMP and Pfr364-LAMP detected 80.2% (81 samples) of the submicroscopic infections using the DNA extraction method by mini spin column kit, while 36.6% (37 samples) were detected using the Boil & Spin sample preparation method.
CONCLUSION
The colorimetric LAMPs with multicopy targets using the COX1 target for P. vivax and the Pfr364 for P. falciparum have a high potential to improve POC malaria diagnosis detecting a greater number of submicroscopic Plasmodium infections.
Topics: Colorimetry; Electron Transport Complex IV; Malaria, Falciparum; Malaria, Vivax; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Plasmodium falciparum; Plasmodium vivax; Protozoan Proteins
PubMed: 34011373
DOI: 10.1186/s12936-021-03753-8 -
The Journal of Infectious Diseases May 2023
Topics: Humans; Plasmodium vivax; Mefloquine; Plasmodium cynomolgi; Antimalarials; Malaria, Vivax; Drug Resistance; Drug Resistance, Multiple
PubMed: 36478038
DOI: 10.1093/infdis/jiac470 -
Pathogens and Global Health May 2015
Topics: DNA, Protozoan; Disease Eradication; Genetic Variation; Host-Parasite Interactions; Humans; Linkage Disequilibrium; Malaria, Vivax; Molecular Diagnostic Techniques; Molecular Epidemiology; Plasmodium vivax
PubMed: 25943154
DOI: 10.1179/2047772415Z.000000000263 -
Briefings in Functional Genomics Sep 2019Plasmodium falciparum and Plasmodium vivax, the two protozoan parasite species that cause the majority of cases of human malaria, have developed resistance to nearly all... (Review)
Review
Plasmodium falciparum and Plasmodium vivax, the two protozoan parasite species that cause the majority of cases of human malaria, have developed resistance to nearly all known antimalarials. The ability of malaria parasites to develop resistance is primarily due to the high numbers of parasites in the infected person's bloodstream during the asexual blood stage of infection in conjunction with the mutability of their genomes. Identifying the genetic mutations that mediate antimalarial resistance has deepened our understanding of how the parasites evade our treatments and reveals molecular markers that can be used to track the emergence of resistance in clinical samples. In this review, we examine known genetic mutations that lead to resistance to the major classes of antimalarial medications: the 4-aminoquinolines (chloroquine, amodiaquine and piperaquine), antifolate drugs, aryl amino-alcohols (quinine, lumefantrine and mefloquine), artemisinin compounds, antibiotics (clindamycin and doxycycline) and a napthoquinone (atovaquone). We discuss how the evolution of antimalarial resistance informs strategies to design the next generation of antimalarial therapies.
Topics: Aminoquinolines; Anti-Bacterial Agents; Antimalarials; Artemisinins; Atovaquone; Drug Resistance; Drug Resistance, Multiple; Folic Acid Antagonists; Humans; Malaria; Plasmodium falciparum; Plasmodium vivax; Quinine
PubMed: 31119263
DOI: 10.1093/bfgp/elz008