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Trends in Parasitology Jun 2020Trager and Jensen established a method for culturing Plasmodium falciparum, a breakthrough for malaria research worldwide. Since then, multiple attempts to establish... (Review)
Review
Trager and Jensen established a method for culturing Plasmodium falciparum, a breakthrough for malaria research worldwide. Since then, multiple attempts to establish Plasmodium vivax in continuous culture have failed. Unlike P. falciparum, which can invade all aged erythrocytes, P. vivax is restricted to reticulocytes. Thus, a constant supply of reticulocytes is considered critical for continuous P. vivax growth in vitro. A critical question remains why P. vivax selectively invades reticulocytes? What do reticulocytes offer to P. vivax that is not present in mature erythrocytes? One possibility is protection from oxidative stress by glucose-6-phosphate dehydrogenase (G6PD). Here, we also suggest supplements to the media and procedures that may reduce oxidative stress and, as a result, establish a system for the continuous culture of P. vivax.
Topics: Culture Techniques; Erythrocytes; Host-Parasite Interactions; Humans; Life Cycle Stages; Oxidative Stress; Plasmodium vivax; Reticulocytes
PubMed: 32360314
DOI: 10.1016/j.pt.2020.04.002 -
Trends in Parasitology Aug 2022The overwhelming dominance of Duffy blood group negativity among most people living in sub-Saharan Africa has been considered the basis of their protection from endemic... (Review)
Review
The overwhelming dominance of Duffy blood group negativity among most people living in sub-Saharan Africa has been considered the basis of their protection from endemic Plasmodium vivax malaria. New evidence demonstrates widespread transmission of P. vivax in Duffy-negative Africa, though currently of unknown distribution, magnitude, or consequences. Other new evidence from outside of Africa demonstrates marked tropisms of P. vivax for extravascular tissues of bone marrow and spleen. Those establish states of proliferative infection with low-grade or undetectable parasitemia of peripheral blood causing acute and chronic disease. This review examines the plausibility of those infectious processes also operating in Duffy-negative Africans and causing harm of unrecognized origin.
Topics: Africa South of the Sahara; Duffy Blood-Group System; Humans; Malaria, Vivax; Parasitemia; Plasmodium vivax
PubMed: 35667992
DOI: 10.1016/j.pt.2022.05.006 -
Immunological Reviews Jan 2020The efficient spread of malaria from infected humans to mosquitoes is a major challenge for malaria elimination initiatives. Gametocytes are the only Plasmodium life... (Review)
Review
The efficient spread of malaria from infected humans to mosquitoes is a major challenge for malaria elimination initiatives. Gametocytes are the only Plasmodium life stage infectious to mosquitoes. Here, we summarize evidence for naturally acquired anti-gametocyte immunity and the current state of transmission blocking vaccines (TBV). Although gametocytes are intra-erythrocytic when present in infected humans, developing Plasmodium falciparum gametocytes may express proteins on the surface of red blood cells that elicit immune responses in naturally exposed individuals. This immune response may reduce the burden of circulating gametocytes. For both P. falciparum and Plasmodium vivax, there is a solid evidence that antibodies against antigens present on the gametocyte surface, when co-ingested with gametocytes, can influence transmission to mosquitoes. Transmission reducing immunity, reducing the burden of infection in mosquitoes, is a well-acknowledged but poorly quantified phenomenon that forms the basis for the development of TBV. Transmission enhancing immunity, increasing the likelihood or intensity of transmission to mosquitoes, is more speculative in nature but is convincingly demonstrated for P. vivax. With the increased interest in malaria elimination, TBV and monoclonal antibodies have moved to the center stage of malaria vaccine development. Methodologies to prioritize and evaluate products are urgently needed.
Topics: Antibodies, Blocking; Antibodies, Protozoan; Host-Parasite Interactions; Humans; Immunity; Immunomodulation; Life Cycle Stages; Malaria Vaccines; Malaria, Falciparum; Malaria, Vivax; Plasmodium falciparum; Plasmodium vivax
PubMed: 31840844
DOI: 10.1111/imr.12828 -
International Journal For Parasitology.... Apr 2021Emerging antimalarial drug resistance may undermine current efforts to control and eliminate Plasmodium vivax, the most geographically widespread yet neglected human... (Review)
Review
Emerging antimalarial drug resistance may undermine current efforts to control and eliminate Plasmodium vivax, the most geographically widespread yet neglected human malaria parasite. Endemic countries are expected to assess regularly the therapeutic efficacy of antimalarial drugs in use in order to adjust their malaria treatment policies, but proper funding and trained human resources are often lacking to execute relatively complex and expensive clinical studies, ideally complemented by ex vivo assays of drug resistance. Here we review the challenges for assessing in vivo P. vivax responses to commonly used antimalarials, especially chloroquine and primaquine, in the presence of confounding factors such as variable drug absorption, metabolism and interaction, and the risk of new infections following successful radical cure. We introduce a simple modeling approach to quantify the relative contribution of relapses and new infections to recurring parasitemias in clinical studies of hypnozoitocides. Finally, we examine recent methodological advances that may render ex vivo assays more practical and widely used to confirm P. vivax drug resistance phenotypes in endemic settings and review current approaches to the development of robust genetic markers for monitoring chloroquine resistance in P. vivax populations.
Topics: Antimalarials; Chloroquine; Humans; Malaria, Vivax; Plasmodium vivax; Primaquine
PubMed: 33360105
DOI: 10.1016/j.ijpddr.2020.12.001 -
Frontiers in Immunology 2022Malaria is one of the most devastating human infectious diseases caused by spp. parasites. A search for an effective and safe vaccine is the main challenge for its... (Review)
Review
Malaria is one of the most devastating human infectious diseases caused by spp. parasites. A search for an effective and safe vaccine is the main challenge for its eradication. is the second most prevalent species and the most geographically distributed parasite and has been neglected for decades. This has a massive gap in knowledge and consequently in the development of vaccines. The most significant difficulties in obtaining a vaccine against are the high genetic diversity and the extremely complex life cycle. Due to its complexity, studies have evaluated antigens from different stages as potential targets for an effective vaccine. Therefore, the main vaccine candidates are grouped into preerythrocytic stage vaccines, blood-stage vaccines, and transmission-blocking vaccines. This review aims to support future investigations by presenting the main findings of vivax malaria vaccines to date. There are only a few vaccines in clinical trials, and thus far, the best protective efficacy was a vaccine formulated with synthetic peptide from a circumsporozoite protein and Montanide ISA-51 as an adjuvant with 54.5% efficacy in a phase IIa study. In addition, the majority of antigen candidates are polymorphic, induce strain-specific and heterogeneous immunity and provide only partial protection. Nevertheless, immunization with recombinant proteins and multiantigen vaccines have shown promising results and have emerged as excellent strategies. However, more studies are necessary to assess the ideal vaccine combination and test it in clinical trials. Developing a safe and effective vaccine against vivax malaria is essential for controlling and eliminating the disease. Therefore, it is necessary to determine what is already known to propose and identify new candidates.
Topics: Humans; Plasmodium vivax; Antigens, Protozoan; Malaria, Vivax; Malaria; Malaria Vaccines; Clinical Trials, Phase II as Topic
PubMed: 36726991
DOI: 10.3389/fimmu.2022.910236 -
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 -
Cell Host & Microbe Dec 2023Vivax malaria has long been thought to be absent from sub-Saharan Africa owing to the high proportion of individuals lacking the Duffy antigen receptor for chemokines...
Vivax malaria has long been thought to be absent from sub-Saharan Africa owing to the high proportion of individuals lacking the Duffy antigen receptor for chemokines (DARC) in their erythrocytes. The interaction between P. vivax Duffy-binding protein (PvDBP) and DARC is assumed to be the main pathway used by merozoites to invade reticulocytes. However, the increasing number of reports of vivax malaria cases in genotypically Duffy-negative (DN) individuals has raised questions regarding the P. vivax invasion pathway(s). Here, we show that a subset of DN erythroblasts transiently express DARC during terminal erythroid differentiation and that P. vivax merozoites, irrespective of their origin, can invade DARC+ DN erythroblasts. These findings reveal that a large number of DN individuals may represent a silent reservoir of deep P. vivax infections at the sites of active erythropoiesis with low or no parasitemia, and it may represent an underestimated biological problem with potential clinical consequences in sub-Saharan Africa.
Topics: Humans; Malaria, Vivax; Antigens, Protozoan; Protozoan Proteins; Plasmodium vivax; Erythrocytes; Duffy Blood-Group System
PubMed: 38056460
DOI: 10.1016/j.chom.2023.11.007 -
Trends in Parasitology May 2020Estimation of Plasmodium vivax biomass based on circulating biomarkers indicates the existence of a predominant biomass outside of the circulation that is not captured... (Review)
Review
Estimation of Plasmodium vivax biomass based on circulating biomarkers indicates the existence of a predominant biomass outside of the circulation that is not captured by peripheral parasitemia, in particular in patients with complicated outcomes. A series of recent studies have suggested that the hematopoietic niche of the bone marrow (BM) is a major reservoir for parasite replication and the development of transmission stages. However, significant knowledge gaps remain in our understanding of host-parasite interactions, pathophysiology, and the implications for treatment and diagnosis of such a reservoir. Here, we discuss the current status of this emerging research field in the context of P. vivax.
Topics: Biomass; Bone Marrow; Hematopoiesis; Host-Parasite Interactions; Humans; Malaria, Vivax; Plasmodium vivax; Research; Reticulocytes
PubMed: 32298632
DOI: 10.1016/j.pt.2020.03.002 -
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