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The Journal of Infectious Diseases May 2021Plasmodium vivax has 2 invasion ligand/host receptor pathways (P. vivax Duffy-binding protein/Duffy antigen receptor for chemokines [DARC] and P. vivax reticulocyte...
Plasmodium vivax has 2 invasion ligand/host receptor pathways (P. vivax Duffy-binding protein/Duffy antigen receptor for chemokines [DARC] and P. vivax reticulocyte binding protein 2b/transferrin receptor [TfR1]) that are promising targets for therapeutic intervention. We optimized invasion assays with isogenic cultured reticulocytes. Using a receptor blockade approach with multiple P. vivax isolates, we found that all strains utilized both DARC and TfR1, but with significant variation in receptor usage. This suggests that P. vivax, like Plasmodium falciparum, uses alternative invasion pathways, with implications for pathogenesis and vaccine development.
Topics: Antigens, CD; Cells, Cultured; Duffy Blood-Group System; Humans; Malaria, Vivax; Plasmodium vivax; Receptors, Cell Surface; Receptors, Transferrin; Reticulocytes
PubMed: 32941614
DOI: 10.1093/infdis/jiaa592 -
Frontiers in Cellular and Infection... 2021Drug resistance in may pose a challenge to malaria elimination. Previous studies have found that has a decreased sensitivity to antimalarial drugs in some areas of the...
Drug resistance in may pose a challenge to malaria elimination. Previous studies have found that has a decreased sensitivity to antimalarial drugs in some areas of the Greater Mekong Sub-region. This study aims to investigate the drug susceptibilities of . isolates from the China-Myanmar border and genetic variations of resistance-related genes. A total of 46 P. clinical isolates were assessed for susceptibility to seven antimalarial drugs using the schizont maturation assay. The medians of IC (half-maximum inhibitory concentrations) for chloroquine, artesunate, and dihydroartemisinin from 46 parasite isolates were 96.48, 1.95, and 1.63 nM, respectively, while the medians of IC values for piperaquine, pyronaridine, mefloquine, and quinine from 39 parasite isolates were 19.60, 15.53, 16.38, and 26.04 nM, respectively. Sequence polymorphisms in (. multidrug resistance-1), (. multidrug resistance protein 1), (. dihydrofolate reductase), and (. dihydropteroate synthase) were determined by PCR and sequencing. had 13 non-synonymous substitutions, of which, T908S and T958M were fixed, G698S (97.8%) and F1076L (93.5%) were highly prevalent, and other substitutions had relatively low prevalences. had three non-synonymous substitutions, with Y1393D being fixed, G1419A approaching fixation (97.8%), and V1478I being rare (2.2%). Several and mutations were relatively frequent in the studied parasite population. The G698S substitution was associated with a reduced sensitivity to chloroquine, artesunate, and dihydroartemisinin. This study suggests the possible emergence of . isolates resistant to certain antimalarial drugs at the China-Myanmar border, which demands continuous surveillance for drug resistance.
Topics: Multidrug Resistance-Associated Proteins; Myanmar; Pharmaceutical Preparations; Plasmodium vivax; Protozoan Proteins
PubMed: 34790586
DOI: 10.3389/fcimb.2021.738075 -
PLoS Medicine Apr 2021Sarah Auburn and co-authors discuss the unique biology and epidemiology of P. vivax and current evidence on conventional and new approaches to surveillance. (Review)
Review
Sarah Auburn and co-authors discuss the unique biology and epidemiology of P. vivax and current evidence on conventional and new approaches to surveillance.
Topics: Epidemiological Monitoring; Humans; Malaria, Vivax; Plasmodium vivax; Population Surveillance
PubMed: 33891580
DOI: 10.1371/journal.pmed.1003560 -
PLoS Pathogens Feb 2020The absence of the Duffy protein at the surface of erythrocytes was considered for decades to confer full protection against Plasmodium vivax as this blood group is the... (Review)
Review
The absence of the Duffy protein at the surface of erythrocytes was considered for decades to confer full protection against Plasmodium vivax as this blood group is the receptor for the key parasite ligand P. vivax Duffy binding protein (PvDBP). However, it is now clear that the parasite is able to break through this protection and induce clinical malaria in Duffy-negative people, although the underlying mechanisms are still not understood. Here, we briefly review the evidence of Duffy-negative infections by P. vivax and summarize the current hypothesis at the basis of this invasion process. We discuss those in the perspective of malaria-elimination challenges, notably in African countries.
Topics: Africa; Antigens, Protozoan; Duffy Blood-Group System; Humans; Malaria, Vivax; Plasmodium vivax; Protozoan Proteins; Receptors, Cell Surface
PubMed: 32078643
DOI: 10.1371/journal.ppat.1008258 -
International Journal For Parasitology.... Aug 2021Plasmodium vivax is the most geographically widespread cause of human malaria and is responsible for the majority of cases outside of the African continent. While great... (Review)
Review
Plasmodium vivax is the most geographically widespread cause of human malaria and is responsible for the majority of cases outside of the African continent. While great progress has been made towards eliminating human malaria, drug resistant parasite strains pose a threat towards continued progress. Resistance has arisen to multiple antimalarials in P. vivax, including to chloroquine, which is currently the first line therapy for P. vivax in most regions. Despite its importance, an understanding of the molecular mechanisms of drug resistance in this species remains elusive, in large part due to the complex biology of P. vivax and the lack of in vitro culture. In this review, we will cover the extent and challenges of measuring clinical and in vitro drug resistance in P. vivax. We will consider the roles of candidate drug resistance genes. We will highlight the development of molecular approaches for studying P. vivax biology that provide the opportunity to validate the role of putative drug resistance mutations as well as identify novel mechanisms of drug resistance in this understudied parasite. Validated molecular determinants and markers of drug resistance are essential for the rapid and cost-effective monitoring of drug resistance in P. vivax, and will be useful for optimizing drug regimens and for informing drug policy in control and elimination settings.
Topics: Antimalarials; Chloroquine; Drug Resistance; Humans; Malaria, Vivax; Plasmodium vivax
PubMed: 33957488
DOI: 10.1016/j.ijpddr.2021.04.002 -
The Korean Journal of Parasitology Dec 2018Plasmodium vivax is more challenging to control and eliminate than P. falciparum due to its more asymptomatic infections with low parasite densities making diagnosis... (Review)
Review
Plasmodium vivax is more challenging to control and eliminate than P. falciparum due to its more asymptomatic infections with low parasite densities making diagnosis more difficult, in addition to its unique biological characteristics. The potential re-introduction of incidence cases, either through borders or via human migrations, is another major hurdle to sustained control and elimination. The Republic of Korea has experienced re-emergence of vivax malaria in 1993 but is one of the 32 malaria-eliminating countries to-date. Despite achieving successful nationwide control and elimination of vivax malaria, the evolutionary characteristics of vivax malaria isolates in the Republic of Korea have not been fully understood. In this review, we present an overview of the genetic variability of such isolates to increase understanding of the epidemiology, diversity, and dynamics of vivax populations in the Republic of Korea.
Topics: Communicable Diseases, Emerging; Epidemics; Genetic Variation; Humans; Malaria, Vivax; Plasmodium vivax; Republic of Korea
PubMed: 30630274
DOI: 10.3347/kjp.2018.56.6.545 -
International Microbiology : the... Sep 2019Malaria is one of the most important human diseases throughout tropical and sub-tropical regions of the world. Global distribution and ample host range have contributed...
Malaria is one of the most important human diseases throughout tropical and sub-tropical regions of the world. Global distribution and ample host range have contributed to the genetic diversity of the etiological agent, Plasmodium. Phylogeographical analyses demonstrated that Plasmodium falciparum and Plasmodium vivax follow an Out of Africa (OOA) expansion, having a higher genetic diversity in African populations and a low genetic diversity in South American populations. Modeling the evolutionary rate of conserved genes for both P. falciparum and P. vivax determined the approximate arrival of human malaria in South America. Bayesian computational methods suggest that P. falciparum originated in Africa and arrived in South America through multiple independent introductions by the transatlantic African slave trade; however, in South America, P. vivax could have been introduced through an alternate migratory route. Alignments of P. vivax mitogenomes have revealed low genetic variation between the South American and Southeast Asian populations suggesting introduction through either pre-Columbian human migration or post-colonization events. To confirm the findings of these phylogeographical analyses, molecular methods were used to diagnose malaria infection in archeological remains of pre-Columbian ethnic groups. Immunohistochemistry tests were used and identified P. vivax but not P. falciparum in histologically prepared tissues from pre-Columbian Peruvian mummies, whereas shotgun metagenomics sequencing of DNA isolated from pre-Columbian Caribbean coprolites revealed Plasmodium-homologous reads; current evidence suggests that only P. vivax might have been present in pre-Columbian South America.
Topics: Caribbean Region; Humans; Malaria, Vivax; Molecular Epidemiology; Phylogeography; Plasmodium vivax; South America
PubMed: 30810995
DOI: 10.1007/s10123-018-00053-1 -
Frontiers in Cellular and Infection... 2021is a genus of apicomplexan parasites which replicate in the liver before causing malaria. can also persist in the liver as dormant hypnozoites and cause clinical...
is a genus of apicomplexan parasites which replicate in the liver before causing malaria. can also persist in the liver as dormant hypnozoites and cause clinical relapse upon activation, but the molecular mechanisms leading to activation have yet to be discovered. In this study, we use high-resolution microscopy to characterize temporal changes of the liver stage tubovesicular network (TVN), a parasitophorous vacuole membrane (PVM)-derived network within the host cytosol. We observe extended membrane clusters, tubules, and TVN-derived vesicles present throughout liver stage development. Additionally, we demonstrate an unexpected presence of the TVN in hypnozoites and observe some association of this network to host nuclei. We also reveal that the host water and solute channel aquaporin-3 (AQP3) associates with TVN-derived vesicles and extended membrane clusters. AQP3 has been previously shown to localize to the PVM of hypnozoites and liver schizonts but has not yet been shown in association to the TVN. Our results highlight host-parasite interactions occur in both dormant and replicating liver stage forms and implicate AQP3 function during this time. Together, these findings enhance our understanding of liver stage biology through characterization of the TVN with an emphasis on the presence of this network in dormant hypnozoites.
Topics: Animals; Liver; Malaria, Vivax; Plasmodium; Plasmodium vivax; Schizonts
PubMed: 34195101
DOI: 10.3389/fcimb.2021.687019 -
Malaria Journal Jul 2020Plasmodium vivax is the predominant Plasmodium species in Afghanistan. National guidelines recommend the combination of chloroquine and primaquine (CQ-PQ) for radical...
BACKGROUND
Plasmodium vivax is the predominant Plasmodium species in Afghanistan. National guidelines recommend the combination of chloroquine and primaquine (CQ-PQ) for radical treatment of P. vivax malaria. Artesunate in combination with the antifolates sulfadoxine-pyrimethamine (SP) has been first-line treatment for uncomplicated falciparum malaria until 2016. Although SP has been the recommended treatment for falciparum and not vivax malaria, exposure of the P. vivax parasite population to SP might still have been quite extensive because of community based management of malaria. The change in the P. vivax antifolate resistance markers between 2007 and 2017 were investigated.
METHODS
Dried blood spots were collected (n = 185) from confirmed P. vivax patients in five malaria-endemic areas of Afghanistan bordering Tajikistan, Turkmenistan and Pakistan, including Takhar, Faryab, Laghman, Nangarhar, and Kunar, in 2007, 2010 and 2017. Semi-nested PCR, RFLP and nucleotide sequencing were used to assess the pyrimethamine resistant related mutations in P. vivax dihydrofolate reductase (pvdhfr I13L, P33L, N50I, F57L, S58R, T61I, S93H, S117N, I173L) and the sulfonamide resistance related mutations in P. vivax dihydropteroate synthase (pvdhps A383G, A553G).
RESULTS
In the 185 samples genotyped for pvdhfr and pvdhps mutations, 11 distinct haplotypes were observed, which evolved over time. In 2007, wild type pvdhfr and pvdhps were the most frequent haplotype in all study sites (81%, 80/99). However, in 2017, the frequency of the wild-type was reduced to 36%, (21/58; p value ≤ 0.001), with an increase in frequency of the double mutant pvdhfr and pvdhps haplotype S58RS117N (21%, 12/58), and the single pvdhfr mutant haplotype S117N (14%, 8/58). Triple and quadruple mutations were not found. In addition, pvdhfr mutations at position N50I (7%, 13/185) and the novel mutation S93H (6%, 11/185) were observed. Based on in silico protein modelling and molecular docking, the pvdhfr N50I mutation is expected to affect only moderately pyrimethamine binding, whereas the S93H mutation does not.
CONCLUSIONS
In the course of ten years, there has been a strong increase in the frequency pyrimethamine resistance related mutations in pvdhfr in the P. vivax population in Afghanistan, although triple and quadruple mutations conferring high grade resistance were not observed. This suggests relatively low drug pressure from SP on the P. vivax parasite population in the study areas. The impact of two newly identified mutations in the pvdhfr gene on pyrimethamine resistance needs further investigation.
Topics: Afghanistan; Antimalarials; Drug Combinations; Drug Resistance; Genetic Markers; Plasmodium vivax; Polymorphism, Genetic; Protozoan Proteins; Pyrimethamine; Sulfadoxine; Tetrahydrofolate Dehydrogenase
PubMed: 32664924
DOI: 10.1186/s12936-020-03319-0 -
Parasites & Vectors Apr 2019Plasmodium vivax contains approximately 5400 coding genes, more than 40% of which code for hypothetical proteins that have not been functionally characterized. In a...
BACKGROUND
Plasmodium vivax contains approximately 5400 coding genes, more than 40% of which code for hypothetical proteins that have not been functionally characterized. In a previous preliminary screening using pooled serum samples, numerous hypothetical proteins were selected from among those that were highly transcribed in the schizont-stage of parasites, and highly antigenic P. vivax candidates including hypothetical proteins were identified. However, their immunological and functional activities in P. vivax remain unclear. From these candidates, we investigated a P. vivax 50-kDa protein (Pv50, PVX_087140) containing a highly conserved signal peptide that shows high transcription levels in blood-stage parasites.
RESULTS
Recombinant Pv50 was expressed in a cell-free expression system and used for IgG prevalence analysis of patients with vivax malaria and healthy individuals. Immune responses were analyzed in immunized mice and mouse antibodies were used to detect the subcellular localization of the protein in blood-stage parasites by immunofluorescence assay. A protein array method was used to evaluate protein-protein interactions to predict protein functional activities during the invasion of parasites into erythrocytes. Recombinant Pv50 showed IgG prevalence in patient samples with a sensitivity of 42.9% and specificity of 93.8% compared to that in healthy individuals. The non-cytophilic antibodies IgG1 and IgG3 were the major components involved in the antibody response in Pv50-immunized mice. Pv50 localized on the surface of merozoites and a specific interaction between Pv50 and PvMSP1 was detected, suggesting that Pv50-PvMSP1 forms a heterodimeric complex in P. vivax.
CONCLUSIONS
Increased immune responses caused by native P. vivax parasites were detected, confirming its immunogenic effects. This study provides a method for detecting new malaria antigens, and Pv50 may be a vivax malaria vaccine candidate with PvMSP1.
Topics: Adolescent; Adult; Animals; Antibodies, Protozoan; Blotting, Western; Cytokines; Female; Humans; Immunity, Humoral; Lymphocyte Count; Malaria, Vivax; Merozoite Surface Protein 1; Merozoites; Mice; Mice, Inbred BALB C; Plasmodium; Plasmodium vivax; Protein Binding; Protozoan Proteins; Recombinant Proteins; T-Lymphocytes; Young Adult
PubMed: 30999945
DOI: 10.1186/s13071-019-3434-7