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Pathogens and Global Health 2016The relapsing peculiarity of Plasmodium vivax is one of the prime reasons for sustained global malaria transmission. Global containment of P. vivax is more challenging... (Review)
Review
The relapsing peculiarity of Plasmodium vivax is one of the prime reasons for sustained global malaria transmission. Global containment of P. vivax is more challenging and crucial compared to other species for achieving total malaria control/elimination. Primaquine (PQ) failure and P. vivax relapse is a major global public health concern. Identification and characterization of different relapse strains of P. vivax prevalent across the globe should be one of the thrust areas in malaria research. Despite renewed and rising global concern by researchers on this once 'neglected' species, research and development on the very topic of P. vivax reappearance remains inadequate. Many malaria endemic countries have not mandated routine glucose-6-phosphate dehydrogenase (G6PD) testing before initiating PQ radical cure in P. vivax malaria. This results in either no PQ prescription or thoughtless prescription and administration of PQ to P. vivax patients by healthcare providers without being concerned about patients' G6PD status and associated complications. It is imperative to ascertain the G6PD status and optimum dissemination of PQ radical cure in all cases of P. vivax malaria across the globe. There persists a compelling need to develop/validate a rapid, easy-to-perform, easy-to-interpret, quality controllable, robust, and cost-effective G6PD assay. High-dose PQ of both standard and short duration appears to be safe and more effective for preventing relapses and should be practiced among patients with normal G6PD activity. Multicentric studies involving adequately representative populations across the globe with reference PQ dose must be carried out to determine the true distribution of PQ failure. Study proving role of cytochrome P450-2D6 gene in PQ metabolism and association of CYP2D6 metabolizer phenotypes and P. vivax relapse is of prime importance and should be carried forward in multicentric systems across the globe.
Topics: Antimalarials; Humans; Malaria, Vivax; Middle Aged; Plasmodium vivax; Primaquine; Recurrence; Treatment Outcome
PubMed: 27077309
DOI: 10.1080/20477724.2015.1133033 -
Frontiers in Cellular and Infection... 2018During the last decade, the vast omics field has revolutionized biological research, especially the genomics, transcriptomics and proteomics branches, as technological... (Review)
Review
During the last decade, the vast omics field has revolutionized biological research, especially the genomics, transcriptomics and proteomics branches, as technological tools become available to the field researcher and allow difficult question-driven studies to be addressed. Parasitology has greatly benefited from next generation sequencing (NGS) projects, which have resulted in a broadened comprehension of basic parasite molecular biology, ecology and epidemiology. Malariology is one example where application of this technology has greatly contributed to a better understanding of spp. biology and host-parasite interactions. Among the several parasite species that cause human malaria, the neglected presents great research challenges, as culturing is not yet feasible and functional assays are heavily limited. Therefore, there are gaps in our biology knowledge that affect decisions for control policies aiming to eradicate vivax malaria in the near future. In this review, we provide a snapshot of key discoveries already achieved in sequencing projects, focusing on developments, hurdles, and limitations currently faced by the research community, as well as perspectives on future vivax malaria research.
Topics: Evolution, Molecular; Gene Expression Profiling; Gene Expression Regulation; Genome, Protozoan; Genomics; Host-Parasite Interactions; Humans; Malaria, Vivax; Metabolome; Metabolomics; Plasmodium vivax; Proteomics
PubMed: 29473024
DOI: 10.3389/fcimb.2018.00034 -
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 -
Frontiers in Cellular and Infection... 2022The neglected but highly prevalent in South-east Asia and South America poses a great challenge, with regards to long-term in-vitro culturing and heavily limited... (Review)
Review
The neglected but highly prevalent in South-east Asia and South America poses a great challenge, with regards to long-term in-vitro culturing and heavily limited functional assays. Such visible challenges as well as narrowed progress in development of experimental research tools hinders development of new drugs and vaccines. The leading vaccine candidate antigen Duffy Binding Protein (DBP), is essential for reticulocyte invasion by binding to its cognate receptor, the Duffy Antigen Receptor for Chemokines (DARC), on the host's reticulocyte surface. Despite its highly polymorphic nature, the amino-terminal cysteine-rich region II of DBP (DBPII) has been considered as an attractive target for vaccine-mediated immunity and has successfully completed the clinical trial Phase 1. Although this molecule is an attractive vaccine candidate against vivax malaria, there is still a question on its viability due to recent findings, suggesting that there are still some aspects which needs to be looked into further. The highly polymorphic nature of DBPII and strain-specific immunity due to DBPII allelic variation in Bc epitopes may complicate vaccine efficacy. Emergence of various blood-stage antigens, such as RBP, EBP and supposedly many more might stand in the way of attaining full protection from DBPII. As a result, there is an urgent need to assess and re-assess various caveats connected to DBP, which might help in designing a long-term promising vaccine for malaria. This review mainly deals with a bunch of rising concerns for validation of DBPII as a vaccine candidate antigen for malaria.
Topics: Antibodies, Protozoan; Antigens, Protozoan; Epitopes; Humans; Malaria, Vivax; Plasmodium vivax; Protein Domains; Protozoan Proteins; Vaccines
PubMed: 35909975
DOI: 10.3389/fcimb.2022.916702 -
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 -
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 -
Frontiers in Cellular and Infection... 2021The control and elimination of malaria caused by both represent a great challenge due to the biological aspects of the species. Gametocytes are the forms responsible...
The control and elimination of malaria caused by both represent a great challenge due to the biological aspects of the species. Gametocytes are the forms responsible for the transmission of the parasite to the vector and the search for new strategies for blocking transmission are essential in a scenario of control and elimination The challenges in this search in regard to mainly stem from the lack of a long-term culture and the limitation of studies of gametocytes. This study evaluated the viability and infectivity of gametocytes in short-term culture. The samples enriched in gametocytes using Percoll (i), using magnetic-activated cell sorting (MACS) (ii), and using non-enriched samples (iii) were evaluated. After the procedures, gametocytes were cultured in IMDM medium for up to 48 h. Cultured gametocytes were viable and infectious for up to 48 h, however differences in viability and infectivity were observed in the samples after 12 h of culture in relation to 0 h. Percoll-enriched samples were shown to be viable in culture for longer intervals than those purified using MACS. Gametocyte viability after enrichment procedures and short-term culture may provide new avenues in the development of methods for evaluating TB.
Topics: Humans; Malaria; Malaria, Vivax; Plasmodium falciparum; Plasmodium vivax
PubMed: 34141630
DOI: 10.3389/fcimb.2021.676276 -
Vaccine Nov 2015In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal... (Review)
Review
In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria.
Topics: Animals; Clinical Trials, Phase III as Topic; Disease Eradication; Humans; Immunity, Cellular; Life Cycle Stages; Malaria Vaccines; Malaria, Falciparum; Malaria, Vivax; Plasmodium falciparum; Plasmodium vivax; Recombinant Proteins; Sporozoites
PubMed: 26324116
DOI: 10.1016/j.vaccine.2015.07.091 -
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