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Proteomics. Clinical Applications Jul 2018Plasmodium vivax is a protozoan parasite that is one of the causative agents of human malaria. Due to several occult features of its life cycle, P. vivax threatens to be... (Review)
Review
Plasmodium vivax is a protozoan parasite that is one of the causative agents of human malaria. Due to several occult features of its life cycle, P. vivax threatens to be a problem for the recent efforts toward elimination of malaria globally. With an emphasis on malaria elimination goals, the authors summarize the major gaps in P. vivax diagnosis and describe how proteomics technologies have begun to contribute toward the discovery of antigens that could be used for various technology platforms and applications. The authors suggest areas where, in the future, proteomics technologies could fill in gaps in P. vivax diagnosis that have proved difficult. The discovery of new parasite antigens, host responses, and immune signatures using proteomics technologies will be a key part of the global malaria elimination efforts.
Topics: Humans; India; Malaria, Vivax; Plasmodium vivax; Proteome; Proteomics; Protozoan Proteins
PubMed: 29193853
DOI: 10.1002/prca.201700024 -
PLoS Neglected Tropical Diseases Aug 2021Understanding epidemiological variables affecting gametocyte carriage and density is essential to design interventions that most effectively reduce malaria...
BACKGROUND
Understanding epidemiological variables affecting gametocyte carriage and density is essential to design interventions that most effectively reduce malaria human-to-mosquito transmission.
METHODOLOGY/PRINCIPAL FINDINGS
Plasmodium falciparum and P. vivax parasites and gametocytes were quantified by qPCR and RT-qPCR assays using the same methodologies in 5 cross-sectional surveys involving 16,493 individuals in Brazil, Thailand, Papua New Guinea, and Solomon Islands. The proportion of infections with detectable gametocytes per survey ranged from 44-94% for P. falciparum and from 23-72% for P. vivax. Blood-stage parasite density was the most important predictor of the probability to detect gametocytes. In moderate transmission settings (prevalence by qPCR>5%), parasite density decreased with age and the majority of gametocyte carriers were children. In low transmission settings (prevalence<5%), >65% of gametocyte carriers were adults. Per survey, 37-100% of all individuals positive for gametocytes by RT-qPCR were positive by light microscopy for asexual stages or gametocytes (overall: P. falciparum 178/348, P. vivax 235/398).
CONCLUSIONS/SIGNIFICANCE
Interventions to reduce human-to-mosquito malaria transmission in moderate-high endemicity settings will have the greatest impact when children are targeted. In contrast, all age groups need to be included in control activities in low endemicity settings to achieve elimination. Detection of infections by light microscopy is a valuable tool to identify asymptomatic blood stage infections that likely contribute most to ongoing transmission at the time of sampling.
Topics: Adolescent; Asymptomatic Diseases; Brazil; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Infant; Malaria, Falciparum; Malaria, Vivax; Male; Papua New Guinea; Plasmodium falciparum; Plasmodium vivax; Thailand; Young Adult
PubMed: 34449764
DOI: 10.1371/journal.pntd.0009672 -
Malaria Journal Nov 2012Understanding the population structure of Plasmodium species through genetic diversity studies can assist in the design of more effective malaria control strategies,...
BACKGROUND
Understanding the population structure of Plasmodium species through genetic diversity studies can assist in the design of more effective malaria control strategies, particularly in vaccine development. Central America is an area where malaria is a public health problem, but little is known about the genetic diversity of the parasite's circulating species. This study aimed to investigate the allelic frequency and molecular diversity of five surface antigens in field isolates from Honduras.
METHODS
Five molecular markers were analysed to determine the genotypes of Plasmodium vivax and Plasmodium falciparum from endemic areas in Honduras. Genetic diversity of ama-1, msp-1 and csp was investigated for P. vivax, and msp-1 and msp-2 for P. falciparum. Allelic frequencies were calculated and sequence analysis performed.
RESULTS AND CONCLUSION
A high genetic diversity was observed within Plasmodium isolates from Honduras. A different number of genotypes were elucidated: 41 (n = 77) for pvama-1; 23 (n = 84) for pvcsp; and 23 (n = 35) for pfmsp-1. Pvcsp sequences showed VK210 as the only subtype present in Honduran isolates. Pvmsp-1 (F2) was the most polymorphic marker for P. vivax isolates while pvama-1 was least variable. All three allelic families described for pfmsp-1 (n = 30) block 2 (K1, MAD20, and RO33), and both allelic families described for the central domain of pfmsp-2 (n = 11) (3D7 and FC27) were detected. However, K1 and 3D7 allelic families were predominant. All markers were randomly distributed across the country and no geographic correlation was found. To date, this is the most complete report on molecular characterization of P. vivax and P. falciparum field isolates in Honduras with regards to genetic diversity. These results indicate that P. vivax and P. falciparum parasite populations are highly diverse in Honduras despite the low level of transmission.
Topics: Antigens, Protozoan; DNA, Protozoan; Gene Frequency; Genetic Variation; Genotype; Honduras; Humans; Malaria, Falciparum; Malaria, Vivax; Molecular Sequence Data; Plasmodium falciparum; Plasmodium vivax; Sequence Analysis, DNA
PubMed: 23181845
DOI: 10.1186/1475-2875-11-391 -
PLoS Neglected Tropical Diseases Jul 2020Plasmodium vivax is the most widespread and difficult to treat cause of human malaria. The development of vaccines against the blood stages of P. vivax remains a key...
Plasmodium vivax is the most widespread and difficult to treat cause of human malaria. The development of vaccines against the blood stages of P. vivax remains a key objective for the control and elimination of vivax malaria. Erythrocyte binding-like (EBL) protein family members such as Duffy binding protein (PvDBP) are of critical importance to erythrocyte invasion and have been the major target for vivax malaria vaccine development. In this study, we focus on another member of EBL protein family, P. vivax erythrocyte binding protein (PvEBP). PvEBP was first identified in Cambodian (C127) field isolates and has subsequently been showed its preferences for binding reticulocytes which is directly inhibited by antibodies. We analysed PvEBP sequence from 316 vivax clinical isolates from eight countries including China (n = 4), Ethiopia (n = 24), Malaysia (n = 53), Myanmar (n = 10), Papua New Guinea (n = 16), Republic of Korea (n = 10), Thailand (n = 174), and Vietnam (n = 25). PvEBP gene exhibited four different phenotypic clusters based on the insertion/deletion (indels) variation. PvEBP-RII (179-479 aa.) showed highest polymorphism similar to other EBL family proteins in various Plasmodium species. Whereas even though PvEBP-RIII-V (480-690 aa.) was the most conserved domain, that showed strong neutral selection pressure for gene purifying with significant population expansion. Antigenicity of both of PvEBP-RII (16.1%) and PvEBP-RIII-V (21.5%) domains were comparatively lower than other P. vivax antigen which expected antigens associated with merozoite invasion. Total IgG recognition level of PvEBP-RII was stronger than PvEBP-RIII-V domain, whereas total IgG inducing level was stronger in PvEBP-RIII-V domain. These results suggest that PvEBP-RII is mainly recognized by natural IgG for innate protection, whereas PvEBP-RIII-V stimulates IgG production activity by B-cell for acquired immunity. Overall, the low antigenicity of both regions in patients with vivax malaria likely reflects genetic polymorphism for strong positive selection in PvEBP-RII and purifying selection in PvEBP-RIII-V domain. These observations pose challenging questions to the selection of EBP and point out the importance of immune pressure and polymorphism required for inclusion of PvEBP as a vaccine candidate.
Topics: Amino Acid Sequence; Antibodies, Protozoan; Asia; Genetic Variation; Humans; Immunity, Humoral; Malaria, Vivax; Plasmodium vivax; Polymorphism, Genetic; Protozoan Proteins; Selection, Genetic; Sequence Alignment
PubMed: 32645098
DOI: 10.1371/journal.pntd.0008202 -
Trends in Parasitology May 2018Plasmodium vivax is the main cause of malarial disease in Asia and South America. Plasmodium vivax infection was thought to be absent in African populations who are... (Review)
Review
Plasmodium vivax is the main cause of malarial disease in Asia and South America. Plasmodium vivax infection was thought to be absent in African populations who are Duffy blood group antigen negative (Duffy-negative). However, many cases of P. vivax infection have recently been observed in Duffy-negative Africans. This raises the question: were P. vivax infections in Duffy-negative populations previously missed or has P. vivax adapted to infect Duffy-negative populations? This review focuses on recent P. vivax findings in Africa and reports views on the parasite ligands that may play a role in Duffy-negative P. vivax infections. In addition, clues gained from studying P. vivax infection of reticulocytes are presented, which may provide possible avenues for establishing P. vivax culture in vitro.
Topics: Adaptation, Physiological; Africa; Duffy Blood-Group System; Erythrocytes; Humans; Ligands; Malaria, Vivax; Plasmodium vivax
PubMed: 29530446
DOI: 10.1016/j.pt.2018.02.006 -
The Journal of Infectious Diseases Apr 2022The presence of Plasmodium vivax malaria parasites in the human bone marrow (BM) is still controversial. However, recent data from a clinical case and experimental...
BACKGROUND
The presence of Plasmodium vivax malaria parasites in the human bone marrow (BM) is still controversial. However, recent data from a clinical case and experimental infections in splenectomized nonhuman primates unequivocally demonstrated the presence of parasites in this tissue.
METHODS
In the current study, we analyzed BM aspirates of 7 patients during the acute attack and 42 days after drug treatment. RNA extracted from CD71+ cell suspensions was used for sequencing and transcriptomic analysis.
RESULTS
We demonstrated the presence of parasites in all patients during acute infections. To provide further insights, we purified CD71+ BM cells and demonstrated dyserythropoiesis and inefficient erythropoiesis in all patients. In addition, RNA sequencing from 3 patients showed that genes related to erythroid maturation were down-regulated during acute infections, whereas immune response genes were up-regulated.
CONCLUSIONS
This study thus shows that during P. vivax infections, parasites are always present in the BM and that such infections induced dyserythropoiesis and ineffective erythropoiesis. Moreover, infections induce transcriptional changes associated with such altered erythropoietic response, thus highlighting the importance of this hidden niche during natural infections.
Topics: Anemia; Animals; Bone Marrow; Erythropoiesis; Humans; Malaria, Vivax; Plasmodium vivax
PubMed: 32556188
DOI: 10.1093/infdis/jiaa177 -
Nature Communications May 2021Despite the high burden of Plasmodium vivax malaria in South Asian countries, the genetic diversity of circulating parasite populations is not well described....
Despite the high burden of Plasmodium vivax malaria in South Asian countries, the genetic diversity of circulating parasite populations is not well described. Determinants of antimalarial drug susceptibility for P. vivax in the region have not been characterised. Our genomic analysis of global P. vivax (n = 558) establishes South Asian isolates (n = 92) as a distinct subpopulation, which shares ancestry with some East African and South East Asian parasites. Signals of positive selection are linked to drug resistance-associated loci including pvkelch10, pvmrp1, pvdhfr and pvdhps, and two loci linked to P. vivax invasion of reticulocytes, pvrbp1a and pvrbp1b. Significant identity-by-descent was found in extended chromosome regions common to P. vivax from India and Ethiopia, including the pvdbp gene associated with Duffy blood group binding. Our investigation provides new understanding of global P. vivax population structure and genomic diversity, and genetic evidence of recent directional selection in this important human pathogen.
Topics: Africa, Eastern; Antimalarials; Asia; Drug Resistance; Duffy Blood-Group System; Genes, Protozoan; Genetic Loci; Humans; Malaria, Vivax; Phylogeny; Phylogeography; Plasmodium vivax; Polymorphism, Single Nucleotide; Protozoan Proteins; Reticulocytes; Selection, Genetic
PubMed: 34039976
DOI: 10.1038/s41467-021-23422-3 -
Malaria Journal Apr 2015Proteins secreted from the rhoptry in Plasmodium merozoites are associated with the formation of tight junctions and parasitophorous vacuoles during invasion of...
BACKGROUND
Proteins secreted from the rhoptry in Plasmodium merozoites are associated with the formation of tight junctions and parasitophorous vacuoles during invasion of erythrocytes and are sorted within the rhoptry neck or bulb. Very little information has been obtained to date about Plasmodium vivax rhoptry-associated leucine (Leu) zipper-like protein 1 (PvRALP1; PVX_096245), a putative rhoptry protein. PvRALP1 contains a signal peptide, a glycine (Gly)/glutamate (Glu)-rich domain, and a Leu-rich domain, all of which are conserved in other Plasmodium species.
METHODS
Recombinant PvRALP1s were expressed as full-length protein without the signal peptide (PvRALP1-Ecto) and as truncated protein consisting of the Gly/Glu- and Leu-rich domains (PvRALP1-Tr) using the wheat germ cell-free expression system. The immunoreactivity to these two fragments of recombinant PvRALP1 protein in serum samples from P. vivax-infected patients and immunized mice, including analysis of immunoglobulin G (IgG) subclasses, was evaluated by enzyme-linked immunosorbent assay or protein microarray technology. The subcellular localization of PvRALP1 in blood stage parasites was also determined.
RESULTS
Recombinant PvRALP1-Ecto and PvRALP1-Tr proteins were successfully expressed, and in serum samples from P. vivax patients from the Republic of Korea, the observed immunoreactivities to these proteins had 58.9% and 55.4% sensitivity and 95.0% and 92.5% specificity, respectively. The response to PvRALP1 in humans was predominantly cytophilic antibodies (IgG1 and IgG3), but a balanced Th1/Th2 response was observed in mice. Unexpectedly, there was no significant inverse correlation between levels of parasitaemia and levels of antibody against either PvRALP1-Ecto (R2=0.11) or PvRALP1-Tr (R2=0.14) antigens. PvRALP1 was localized in the rhoptry neck of merozoites, and this was the first demonstration of the localization of this protein in P. vivax.
CONCLUSIONS
This study analysed the antigenicity and immunogenicity of PvRALP1 and suggested that PvRALP1 may be immunogenic in humans during parasite infection and might play an important role during invasion of P. vivax parasites.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Enzyme-Linked Immunosorbent Assay; Humans; Immunoglobulin G; Malaria, Vivax; Merozoites; Mice; Mice, Inbred BALB C; Middle Aged; Plasmodium vivax; Protein Array Analysis; Protozoan Proteins; Rabbits; Recombinant Proteins; Republic of Korea; Young Adult
PubMed: 25925592
DOI: 10.1186/s12936-015-0698-z -
Cellular Microbiology Jan 2020Plasmodium vivax is responsible for most of the malaria infections outside Africa and is currently the predominant malaria parasite in countries under elimination... (Review)
Review
Plasmodium vivax is responsible for most of the malaria infections outside Africa and is currently the predominant malaria parasite in countries under elimination programs. P. vivax preferentially enters young red cells called reticulocytes. Advances in understanding the molecular and cellular mechanisms of entry are hampered by the inability to grow large numbers of P. vivax parasites in a long-term in vitro culture. Recent progress in understanding the biology of the P. vivax Reticulocyte Binding Protein (PvRBPs) family of invasion ligands has led to the identification of a new invasion pathway into reticulocytes, an understanding of their structural architecture and PvRBPs as targets of the protective immune response to P. vivax infection. This review summarises current knowledge on the role of reticulocytes in P. vivax infection, the function of the PvRBP family of proteins in generating an immune response in human populations, and the characterization of anti-PvRBP antibodies in blocking parasite invasion.
Topics: Antibodies, Protozoan; Humans; Malaria, Vivax; Membrane Proteins; Plasmodium vivax; Protein Binding; Protozoan Proteins; Reticulocytes
PubMed: 31469946
DOI: 10.1111/cmi.13110 -
Scientific Reports Jun 2018Malaria control program in the Arabian Peninsula, backed by adequate logistical support, has interrupted transmission with exception of limited sites in Saudi Arabia and...
Malaria control program in the Arabian Peninsula, backed by adequate logistical support, has interrupted transmission with exception of limited sites in Saudi Arabia and sporadic outbreaks in Oman. However, sustained influx of imported malaria represents a direct threat to the above success. Here we examined the extent of genetic diversity among imported P. vivax in Qatar, and its ability to produce gametocytes, compared to parasites in main sites of imported cases, the Indian subcontinent (india) and East Africa (Sudan and Ethiopia). High diversity was seen among imported P. vivax in Qatar, comparable to parasites in the Indian subcontinent and East Africa. Limited genetic differentiation was seen among imported P. vivax, which overlapped with parasites in India, but differentiated from that in Sudan and Ethiopia. Parasite density among imported cases, ranged widely between 26.25-7985934.1 Pv18S rRNA copies/µl blood, with a high prevalence of infections carried gametocytes detectable by qRT-PCR. Parasitaemia was a stronger predictor for P. vivax gametocytes density (r = 0.211, P = 0.04). The extensive diversity of imported P. vivax and its ability to produce gametocytes represent a major threat for re-introduction of malaria in Qatar. The genetic relatedness between P. vivax reported in Qatar and those in India suggest that elimination strategy should target flow and dispersal of imported malaria into the region.
Topics: Africa, Eastern; Communicable Diseases, Imported; Disease Transmission, Infectious; Genetic Variation; Genotype; Humans; India; Malaria, Vivax; Molecular Epidemiology; Parasite Load; Plasmodium vivax; Qatar; RNA, Protozoan; RNA, Ribosomal, 18S; Real-Time Polymerase Chain Reaction
PubMed: 29891983
DOI: 10.1038/s41598-018-27229-z