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PloS One 2012Plasmodium vivax infections seldom kill directly but do cause indirect mortality by reducing birth weight and causing abortion. Cytoadherence and sequestration in the...
BACKGROUND
Plasmodium vivax infections seldom kill directly but do cause indirect mortality by reducing birth weight and causing abortion. Cytoadherence and sequestration in the microvasculature are central to the pathogenesis of severe Plasmodium falciparum malaria, but the contribution of cytoadherence to pathology in other human malarias is less clear.
METHODOLOGY
The adherence properties of P. vivax infected red blood cells (PvIRBC) were evaluated under static and flow conditions.
PRINCIPAL FINDINGS
P. vivax isolates from 33 patients were studied. None adhered to immobilized CD36, ICAM-1, or thrombospondin, putative ligands for P. falciparum vascular cytoadherence, or umbilical vein endothelial cells, but all adhered to immobilized chondroitin sulphate A (CSA) and hyaluronic acid (HA), the receptors for adhesion of P. falciparum in the placenta. PvIRBC also adhered to fresh placental cells (N = 5). Pre-incubation with chondroitinase prevented PvIRBC adherence to CSA, and reduced binding to HA, whereas preincubation with hyaluronidase prevented adherence to HA, but did not reduce binding to CSA significantly. Pre-incubation of PvIRBC with soluble CSA and HA reduced binding to the immobilized receptors and prevented placental binding. PvIRBC adhesion was prevented by pre-incubation with trypsin, inhibited by heparin, and reduced by EGTA. Under laminar flow conditions the mean (SD) shear stress reducing maximum attachment by 50% was 0.06 (0.02) Pa but, having adhered, the PvIRBC could then resist detachment by stresses up to 5 Pa. At 37 °C adherence began approximately 16 hours after red cell invasion with maximal adherence at 30 hours. At 39 °C adherence began earlier and peaked at 24 hours.
SIGNIFICANCE
Adherence of P. vivax-infected erythrocytes to glycosaminoglycans may contribute to the pathogenesis of vivax malaria and lead to intrauterine growth retardation.
Topics: Adult; Cell Adhesion; Chondroitin Sulfates; Egtazic Acid; Erythrocytes; Female; Glycosaminoglycans; Heparin; Humans; Hyaluronic Acid; Malaria, Vivax; Placenta; Plasmodium vivax; Pregnancy; Temperature; Trypsin
PubMed: 22529919
DOI: 10.1371/journal.pone.0034509 -
PloS One 2011Plasmodium vivax is considered to be rare in the predominantly Duffy negative populations of Sub-Saharan Africa, as this red blood cell surface antigen is essential for...
Plasmodium vivax is considered to be rare in the predominantly Duffy negative populations of Sub-Saharan Africa, as this red blood cell surface antigen is essential for invasion by the parasite. However, despite only very few reports of molecularly confirmed P. vivax from tropical Africa, serological evidence indicated that 13% of the persons sampled in Congo had been exposed to P. vivax. We identified P. vivax by microscopy in 8 smears from Ugandan pregnant women who had been enrolled in a longitudinal study of malaria in pregnancy. A nested polymerase chain reaction (PCR) protocol was used to detect and identify the Plasmodium parasites present. PCR analysis confirmed the presence of P. vivax for three of the women and analysis of all available samples from these women revealed clinically silent chronic low-grade vivax infections for two of them. The parasites in one woman carried pyrimethamine resistance-associated double non-synonymous mutations in the P. vivax dihydrofolate reductase gene. The three women found infected with P. vivax were Duffy positive as were nine of 68 women randomly selected from the cohort. The data presented from these three case reports is consistent with stable transmission of malaria in a predominantly Duffy negative African population. Given the substantial morbidity associated with vivax infection in non-African endemic areas, it will be important to investigate whether the distribution and prevalence of P. vivax have been underestimated in Sub-Saharan Africa. This is particularly important in the context of the drive to eliminate malaria and its morbidity.
Topics: Africa South of the Sahara; Cohort Studies; Drug Resistance; Duffy Blood-Group System; Erythrocytes; Female; Humans; Longitudinal Studies; Malaria, Vivax; Plasmodium vivax; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications, Parasitic; Uganda
PubMed: 21603649
DOI: 10.1371/journal.pone.0019801 -
PLoS Biology May 2020Plasmodium vivax and P. falciparum, the parasites responsible for most human malaria worldwide, exhibit striking biological differences, which have important clinical...
Plasmodium vivax and P. falciparum, the parasites responsible for most human malaria worldwide, exhibit striking biological differences, which have important clinical consequences. Unfortunately, P. vivax, unlike P. falciparum, cannot be cultivated continuously in vitro, which limits our understanding of its biology and, consequently, our ability to effectively control vivax malaria. Here, we describe single-cell gene expression profiles of 9,215 P. vivax parasites from bloodstream infections of Aotus and Saimiri monkeys. Our results show that transcription of most P. vivax genes occurs during short periods of the intraerythrocytic cycle and that this pattern of gene expression is conserved in other Plasmodium species. However, we also identify a strikingly high proportion of species-specific transcripts in late schizonts, possibly associated with the specificity of erythrocyte invasion. Our findings provide new and robust markers of blood-stage parasites, including some that are specific to the elusive P. vivax male gametocytes, and will be useful for analyzing gene expression data from laboratory and field samples.
Topics: Animals; Aotidae; Chloroquine; Female; Gene Expression; Male; Multigene Family; Plasmodium vivax; Saimiri; Schizonts; Sequence Analysis, RNA; Single-Cell Analysis; Species Specificity; Transcriptome
PubMed: 32365102
DOI: 10.1371/journal.pbio.3000711 -
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 -
The Korean Journal of Parasitology Oct 2017Recent trends of malaria in Thailand illustrate an increasing proportion of Plasmodium vivax, indicating the importance of P. vivax as a major causative agent of...
Recent trends of malaria in Thailand illustrate an increasing proportion of Plasmodium vivax, indicating the importance of P. vivax as a major causative agent of malaria. P. vivax malaria is usually considered a benign disease so the knowledge of this parasite has been limited, especially the genetic diversity and genetic structure of isolates from different endemic areas. The aim of this study was to examine the population genetics and structure of P. vivax isolates from 4 provinces with different malaria endemic settings in Thailand using 6 microsatellite markers. Total 234 blood samples from P. vivax mono-infected patients were collected. Strong genetic diversity was observed across all study sites; the expected heterozygosity values ranged from 0.5871 to 0.9033. Genetic variability in this study divided P. vivax population into 3 clusters; first was P. vivax isolates from Mae Hong Son and Kanchanaburi Provinces located on the western part of Thailand; second, Yala isolates from the south; and third, Chanthaburi isolates from the east. P. vivax isolates from patients having parasite clearance time (PCT) longer than 24 hr after the first dose of chloroquine treatment had higher diversity when compared with those having PCT within 24 hr. This study revealed a clear evidence of different population structure of P. vivax from different malaria endemic areas of Thailand. The findings provide beneficial information to malaria control programme as it is a useful tool to track the source of infections and current malaria control efforts.
Topics: Female; Genetic Variation; Humans; Malaria, Vivax; Male; Microsatellite Repeats; Plasmodium vivax; Thailand
PubMed: 29103261
DOI: 10.3347/kjp.2017.55.5.465 -
The Journal of Infectious Diseases Dec 1993A Plasmodium vivax-like human malaria parasite was recently identified from Madang, a holoendemic malarious region in Papua New Guinea. The complete nucleotide sequence...
A Plasmodium vivax-like human malaria parasite was recently identified from Madang, a holoendemic malarious region in Papua New Guinea. The complete nucleotide sequence of the circumsporozoite (CS) protein gene of this parasite is presented here. The CS protein of this parasite has an 11-mer repeat sequence and is different from the other known CS protein genes of human malaria parasites. However, it is identical to the CS protein gene of a monkey malaria parasite, Plasmodium simiovale. This P. vivax-like malaria parasite was found in Sepik, another malarious region of Papua New Guinea, and in Brazil, Indonesia, and Madagascar. No pure isolate of this parasite was identified. Specific oligonucleotide probes were used to determine relative proportion of the P. vivax-like parasite in P. vivax (type 1 and type 2) mixed field isolates. Compared with P. vivax or Plasmodium falciparum, the circumsporozoite protein of P. vivax-like parasites showed markedly less polymorphism.
Topics: Amino Acid Sequence; Animals; Base Sequence; DNA, Protozoan; Humans; Malaria, Vivax; Molecular Sequence Data; Plasmodium vivax; Protozoan Proteins; Repetitive Sequences, Nucleic Acid; Sequence Homology, Nucleic Acid
PubMed: 8245533
DOI: 10.1093/infdis/168.6.1485 -
The American Journal of Tropical... Aug 2001Chloroquine-resistant Plasmodium vivax has been the subject of numerous case reports and prospective studies from Oceania and Asia. In contrast, only case reports exist... (Clinical Trial)
Clinical Trial
Chloroquine-resistant Plasmodium vivax has been the subject of numerous case reports and prospective studies from Oceania and Asia. In contrast, only case reports exist from the Americas. We performed a prospective study with 28-day follow-up of clinical responses to chloroquine in 2 P. vivax-endemic regions of Colombia. Three (11%) of 27 patients failed to respond to treatment with the standard regimen of chloroquine (1,500 mg of base over 3 days). One patient demonstrated RI resistance on Day 26; one patient demonstrated RI resistance due to recrudescence of blood stages on Day 11; and one patient demonstrated RII resistance of blood stages by never displaying clearing of peripheral parasitemia. All patients were successfully treated with primaquine, which has some blood stage efficacy against P. vivax, combined with a second course of chloroquine. Clinical resistance of P. vivax to chloroquine is present in Colombia and should be monitored in the Americas.
Topics: Animals; Antimalarials; Chloroquine; Colombia; Drug Therapy, Combination; Humans; Malaria, Vivax; Male; Parasitemia; Plasmodium vivax; Primaquine; Treatment Failure
PubMed: 11508397
DOI: 10.4269/ajtmh.2001.65.90 -
Malaria Journal Mar 2022Anti-malarial drug resistance is still a major threat to malaria elimination in the Great Mekong Sub-region. Plasmodium vivax parasites resistant to anti-malarial drugs...
BACKGROUND
Anti-malarial drug resistance is still a major threat to malaria elimination in the Great Mekong Sub-region. Plasmodium vivax parasites resistant to anti-malarial drugs are now found in Myanmar. Molecular surveillance on drug resistance genes in P. vivax parasites from northeastern Myanmar was aimed at estimating the underlying drug resistance in this region.
METHODS
Blood samples from patients with vivax malaria were collected from Laiza city in northeastern Myanmar in 2020. Drug resistance genes including Pvcrt-o, Pvmdr1, Pvdhfr and Pvdhps were amplified and sequenced. Genetic polymorphisms and haplotypes were analysed to evaluate the prevalence of mutant alleles associated with drug resistance.
RESULTS
A total of 149 blood samples from P. vivax patients were collected. The prevalence of Pvmdr1 mutations at codons 958 and 1076 was 100.0% and 52.0%, respectively, whereas no single nucleotide polymorphism was present at codon 976. The proportions of single and double mutant types were 48.0% and 52.0%, respectively. A K10 "AAG" insertion in the Pvcrt-o gene was not detected. Mutations in Pvdhfr at codons 57, 58, 61, 99 and 117 were detected in 29.9%, 54.3%, 27.6%, 44.9% and 55.1% of the samples, respectively. Wild type was predominant (46.3%), followed by quadruple and double mutant haplotypes. Of three types of tandem repeat variations of Pvdhfr, Type B, with three copies of GGDN repeats, was the most common. Pvdhps mutations were only detected at codons 383 and 553 and the wild type Pvdhps was dominant (78.0%). Eleven haplotypes were identified when combining the mutations of Pvdhfr and Pvdhps, among which the predominant one was the wild type (33.9%), followed by double mutant alleles S58R/S117N /WT (24.6%).
CONCLUSIONS
This study demonstrated resistant P. vivax phenotypes exists in northeastern Myanmar. Continued surveillance of drug resistance markers is needed to update treatment guidelines in this region.
Topics: Antimalarials; Drug Resistance; Humans; Malaria, Vivax; Mutation; Myanmar; Plasmodium vivax; Polymorphism, Single Nucleotide; Protozoan Proteins
PubMed: 35241080
DOI: 10.1186/s12936-022-04084-y -
Malaria Journal May 2017Relapse infections resulting from the activation hypnozoites produced by Plasmodium vivax and Plasmodium ovale represent an important obstacle to the successful control...
BACKGROUND
Relapse infections resulting from the activation hypnozoites produced by Plasmodium vivax and Plasmodium ovale represent an important obstacle to the successful control of these species. A single licensed drug, primaquine is available to eliminate these liver dormant forms. To date, investigations of vivax relapse infections have been few in number.
RESULTS
Genotyping, based on polymorphic regions of two genes (Pvmsp1F3 and Pvcsp) and four microsatellite markers (MS3.27, MS3.502, MS6 and MS8), of 12 paired admission and relapse samples from P. vivax-infected patients were treated with primaquine, revealed that in eight of the parasite populations in the admission and relapse samples were homologous, and heterologous in the remaining four patients. The patients' CYP2D6 genotypes did not suggest that any were poor metabolisers of primaquine. Parasitaemia tended to be higher in the heterologous as compared to the homologous relapse episodes as was the IgG3 response. For the twelve pro- and anti-inflammatory cytokine levels measured for all samples, only those of IL-6 and IL-10 tended to be higher in patients with heterologous as compared to homologous relapses in both admission and relapse episodes.
CONCLUSIONS
The data from this limited number of patients with confirmed relapse episodes mirror previous observations of a significant proportion of heterologous parasites in relapses of P. vivax infections in Thailand. Failure of the primaquine treatment that the patients received is unlikely to be due to poor drug metabolism, and could indicate the presence of P. vivax populations in Thailand with poor susceptibility to 8-aminoquinolines.
Topics: Adolescent; Adult; Antimalarials; Cohort Studies; Drug Resistance; Follow-Up Studies; Genotype; Humans; Malaria, Vivax; Middle Aged; Plasmodium vivax; Primaquine; Recurrence; Thailand; Young Adult
PubMed: 28558712
DOI: 10.1186/s12936-017-1877-x -
Malaria Journal Jul 2015Plasmodium vivax is the second most prevalent human malaria parasite in Bangladesh; however, there are no data of its genetic diversity. Several molecular markers are...
BACKGROUND
Plasmodium vivax is the second most prevalent human malaria parasite in Bangladesh; however, there are no data of its genetic diversity. Several molecular markers are available where Pvcsp, Pvmsp 1 and Pvmsp 3α are most commonly used for P. vivax genotyping studies. The aim of the study was to investigate the population structure of P. vivax in Bangladesh.
METHODS
A total of 102 P. vivax-positive blood samples were collected from different malaria-endemic areas in Bangladesh and subsequently analysed for those three genotyping markers. Nested PCR was performed for diagnosis and genotyping analysis followed by PCR-RFLP to detect genetic diversity using Pvcsp, Pvmsp 1 and Pvmsp 3α markers.
RESULTS
Analysis of Pvcsp showed that the VK210 repeat type was highly prevalent (64.7%, 66/102) compared to VK247 (35.3%, 36/102), although the prevalence of VK247 was higher than other Southeast Asian countries. Analysis of these three genes revealed a diverse, circulating population of P. vivax where a total of ten, 56 and 35 distinct genotypes were detected for Pvcsp, Pvmsp 1 and Pvmsp 3α, respectively.
CONCLUSION
This genotyping observation of P. vivax is the first report from Bangladesh and will provide valuable information for establishing the genotyping methods and circulating genetic variants of these three markers available in Bangladesh.
Topics: Adolescent; Adult; Antigens, Protozoan; Bangladesh; Child; Child, Preschool; Female; Humans; Male; Merozoite Surface Protein 1; Middle Aged; Plasmodium vivax; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Protozoan Proteins; Young Adult
PubMed: 26159168
DOI: 10.1186/s12936-015-0790-4