Diversity of vir Genes in Plasmodium vivax from Endemic Regions in the Republic of Korea: an Initial Evaluation.
Ontology highlight
ABSTRACT:
SUBMITTER: Son UH
PROVIDER: S-EPMC5452439 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundPlasmodium vivax proteins with variant interspersed repeats (VIR) are the key proteins used by the parasite to escape from the host immune system through the creation of antigenic variations. However, few studies have been done to elucidate their role as targets of immunity. Thus, this study evaluated the naturally-acquired immune response against VIR proteins in vivax malaria-infected individuals in the Republic of Korea (ROK).MethodsSeven recombinant VIR proteins and two synthetic peptides previously studied in other countries that elicited a robust immune response were used to investigate the antibody and cellular immune response in 681 P. vivax-infected people in ROK. The expression of IgM, IgG, and IgG subclasses against each VIR antigen or against PvMSP1-19 was analysed by ELISA. PvMSP1-19, known as a promising vaccine candidate of P. vivax, was used as the positive control for immune response assessment. Furthermore, the cellular immune response to VIR antigens was evaluated by in vitro proliferative assay, cellular activation assay, and cytokine detection in mononuclear cells of the P. vivax-infected population.ResultsIgM or IgG were detected in 52.4% of the population. Among all the VIR antigens, VIR25 elicited the highest humoral immune response in the whole population with IgG and IgM prevalence of 27.8% and 29.2%, respectively, while PvMSP1-19 elicited even higher prevalence (92%) of IgG in the population. As for the cellular immune response, VIR-C2, PvLP2, and PvMSP1-19 induced high cell activation and secretion of IL-2, IL-6, IL-10, and G-CSF in mononuclear cells from the P. vivax-infected population, comparable with results from PvMSP1-19. However, no significant proliferation response to these antigens was observed between the malaria-infected and healthy groups.ConclusionModerate natural acquisition of antibody and cellular responses in P. vivax-infected Korean malaria patients presented here are similar to that in other countries. It is interesting that the immune response to VIR antigens is conserved among malaria parasites in different countries, considering that VIR genes are highly polymorphic. This thus warrants further studies to elucidate molecular mechanisms by which human elicit immune response to the malaria parasite VIR antigens.
| S-EPMC8237554 | biostudies-literature
Project description:BackgroundThe reemergence of Plasmodium vivax in South Korea since 1993 represents a serious public health concern. Despite the importance in understanding genetic diversity for control strategies, however, studies remain inconclusive with the general premise that due to low rate of malaria transmission, there is generally low genetic diversity with very few strains involved. In this study, the genetic diversity and population structure of P. vivax in South Korea were explored by analysing microsatellite polymorphism.MethodsSequences for 13 microsatellite loci distributed across the twelve chromosomes of P. vivax were obtained from 58 South Korean isolates collected during two sampling periods, namely 1997-2000 and 2007. The sequences were used for the analysis of expected heterozygosity and multilocus genotype diversity. Population structure was evaluated using STRUCTURE version 2.3.2. Linkage disequilibrium was also analysed to investigate the extent of outbreeding in the P. vivax population.ResultsMean expected heterozygosity significantly increased from 0.382 in 1997-2000 to 0.545 in 2007 (P < 0.05). The number of multilocus genotypes was 7 and 27; and genotype diversity was statistically significant (P < 0.01) at 0.661 and 0.995 in 1997-2000 and 2007, respectively. Analysis by STRUCTURE showed a more complex population structure in 2007 than in 1997-2000. Linkage disequilibrium between 13 microsatellites, although significant in both time points, was notably lower in 2007.ConclusionsThe present microsatellite analysis clearly showed recent increase of genetic diversity and recent relaxation of the strong population structure observed in 1997-2000. These results suggest that multiple genotypes not present previously recently migrated into South Korea, accompanied by substantial outbreeding between different genotypes.
| S-EPMC3176257 | biostudies-literature
Project description:BackgroundVivax malaria was successfully eliminated from the Republic of Korea (ROK) in the late 1970s but re-emerged in 1993. Two decades later as the ROK enters the final stages of malaria elimination, dedicated surveillance of the local P. vivax population is critical. We apply a population genetic approach to gauge P. vivax transmission dynamics in the ROK between 2010 and 2012.Methodology/principal findingsP. vivax positive blood samples from 98 autochthonous cases were collected from patients attending health centers in the ROK in 2010 (n = 27), 2011 (n = 48) and 2012 (n = 23). Parasite genotyping was undertaken at 9 tandem repeat markers. Although not reaching significance, a trend of increasing population diversity was observed from 2010 (HE = 0.50 ± 0.11) to 2011 (HE = 0.56 ± 0.08) and 2012 (HE = 0.60 ± 0.06). Conversely, linkage disequilibrium declined during the same period: IAS = 0.15 in 2010 (P = 0.010), 0.09 in 2011 (P = 0.010) and 0.05 in 2012 (P = 0.010). In combination with data from other ROK studies undertaken between 1994 and 2007, our results are consistent with increasing parasite divergence since re-emergence. Polyclonal infections were rare (3% infections) suggesting that local out-crossing alone was unlikely to explain the increased divergence. Cases introduced from an external reservoir may therefore have contributed to the increased diversity. Aside from one isolate, all infections carried a short MS20 allele (142 or 149 bp), not observed in other studies in tropical endemic countries despite high diversity, inferring that these regions are unlikely reservoirs.ConclusionsWhilst a number of factors may explain the observed population genetic trends, the available evidence suggests that an external geographic reservoir with moderate diversity sustains the majority of P. vivax infection in the ROK, with important implications for malaria elimination.
| S-EPMC4798397 | biostudies-literature
Project description:BackgroundThe naturally-acquired immune response to Plasmodium vivax variant antigens (VIR) was evaluated in individuals exposed to malaria and living in different endemic areas for malaria in the north of Brazil.MethodsSeven recombinant proteins representing four vir subfamilies (A, B, C, and E) obtained from a single patient from the Amazon Region were expressed in Escherichia coli as soluble glutathione S-transferase fusion proteins. The different recombinant proteins were compared by ELISA with regard to the recognition by IgM, IgG, and IgG subclass of antibodies from 200 individuals with patent infection.ResultsThe frequency of individuals that presented antibodies anti-VIR (IgM plus IgG) during the infection was 49%. The frequencies of individuals that presented IgM or IgG antibodies anti-VIR were 29.6% or 26.0%, respectively. The prevalence of IgG antibodies against recombinant VIR proteins was significantly lower than the prevalence of antibodies against the recombinant proteins representing two surface antigens of merozoites of P. vivax: AMA-1 and MSP119 (57.0% and 90.5%, respectively). The cellular immune response to VIR antigens was evaluated by in vitro proliferative assays in mononuclear cells of the individuals recently exposed to P. vivax. No significant proliferative response to these antigens was observed when comparing malaria-exposed to non-exposed individuals.ConclusionThis study provides evidence that there is a low frequency of individuals responding to each VIR antigens in endemic areas of Brazil. This fact may explain the host susceptibility to new episodes of the disease.
| S-EPMC1626480 | biostudies-literature
Project description:Malaria has persisted as an endemic near the Demilitarized Zone in the Republic of Korea since the re-emergence of Plasmodium vivax malaria in 1993. The number of patients affected by malaria has increased recently despite many controls tools, one of the reasons behind which is the relapse of malaria via liver hypnozoites. Tafenoquine, a new drug approved by the United States Food and Drug Administration in 2018, is expected to reduce the rate of relapse of malaria hypnozoites and thereby decrease the prevalence of malaria among the population. In this work, we have developed a new transmission model for Plasmodium vivax that takes into account a more realistic intrinsic distribution from existing literature to quantify the current values of relapse parameters and to evaluate the effectiveness of the anti-relapse therapy. The model is especially suitable for estimating parameters near the Demilitarized Zone in Korea, in which the disease follows a distinguishable seasonality. Results were shown that radical cure could significantly reduce the prevalence level of malaria. However, eradication would still take a long time (over 10 years) even if the high-level treatment were to persist. In addition, considering that the vector's behavior is manipulated by the malaria parasite, relapse repression through vector control at the current level may result in a negative effect in containing the disease. We conclude that the use of effective drugs should be considered together with the increased level of the vector control to reduce malaria prevalence.
| S-EPMC6980521 | biostudies-literature
Project description:BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency is the most prevalent inborn disorder. This X-chromosome-linked recessive disease affects more than 400 million people globally, and is associated with haemolytic anaemia after medication with the anti-latent malaria drug, primaquine. To prevent malaria, the Republic of Korea (ROK) Army administers malaria chemoprophylaxis. Due to the previously low G6PD deficiency prevalence in the ROK, prior to primaquine administration, testing for G6PD deficiency was not mandatory. In this study, to evaluate the risk from malaria chemoprophylaxis in the ROK, G6PD deficiency prevalence was investigated.MethodsBlood specimens from 1632 soldiers entering training camp for the 3rd Infantry of the ROK Army were collected. CareStart™ Biosensor for G6PD and haemoglobin (Hb) was used to detect G6PD levels. G6PD variants using the DiaPlexC G6PD Genotyping kit (Asian type) and full-length sequencing were examined.ResultsOf 1632 blood specimens tested, none was observed to be G6PD deficient. The median value of all tested samples was 7.582 U/g Hb. An investigation of 170 G6PD DNA variants was analysed and categorized as partially low normal [n = 131, 30-80% (2.27-6.05 U/g Hb) of the median value], high [n = 3, > 150% (> 11.373 U/g Hb) of the median value], or normal [n = 36, 80-150% (6.05-11.373 U/g Hb) of the median value], and none was amplified by the DiaPlexC kit. Five silent mutations (C→T) in 131 partially low normal specimens were found at the 1311th nucleotide position by sequence analysis. Another 8 silent mutations (T93C) were also detected in 131 partially low normal specimens. Thus, it is inferred that these silent mutations could be related to G6PD activity.ConclusionsThis G6PD deficiency prevalence study, conducted among participants from the 3rd Infantry of the ROK Army, provided crucial evidence for the safety of malaria chemoprophylaxis. This study showed that the prevalence of G6PD deficiency among 1632 young soldiers was wholly absent. Although G6PD phenotypic mutations were not detected, many silent mutations (C1311T and T93C) were observed. Thus, it is inferred that malaria chemoprophylaxis is relatively safe against G6PD deficiency-mediated haemolytic anaemia. However, given the number of individuals whose G6PD were at the partially low normal range and the frequent detection of G6PD deficiency-related mutations, consistent monitoring of G6PD deficiency is needed.
| S-EPMC7465311 | biostudies-literature
Project description:Plasmodium vivax is a major challenge for malaria control due to its wide geographic distribution, high frequency of submicroscopic infections, and ability to induce relapses due to the latent forms present in the liver (hypnozoites). Deepening our knowledge of parasite biology and its molecular components is key to develop new tools for malaria control and elimination. This study aims to investigate and characterize a P. vivax protein (PvVir14) for its role in parasite biology and its interactions with the immune system. We collected sera or plasma from P.vivax-infected subjects in Brazil (n = 121) and Cambodia (n = 55), and from P. falciparum-infected subjects in Mali (n = 28), to assess antibody recognition of PvVir14. Circulating antibodies against PvVir14 appeared in 61% and 34.5% of subjects from Brazil and Cambodia, respectively, versus none (0%) of the P. falciparum-infected subjects from Mali who have no exposure to P. vivax. IgG1 and IgG3 most frequently contributed to anti-PvVir14 responses. PvVir14 antibody levels correlated with those against other well-characterized sporozoite/liver (PvCSP) and blood stage (PvDBP-RII) antigens, which were recognized by 7.6% and 42% of Brazilians, respectively. Concerning the cellular immune profiling of Brazilian subjects, PvVir14 seroreactive individuals displayed significantly higher levels of circulating atypical (CD21- CD27-) B cells, raising the possibility that atypical B cells may be contribute to the PvVir14 antibody response. When analyzed at a single-cell level, the B cell receptor gene hIGHV3-23 was only seen in subjects with active P.vivax infection where it comprised 20% of V gene usage. Among T cells, CD4+ and CD8+ levels differed (lower and higher, respectively) between subjects with versus without antibodies to PvVir14, while NKT cell levels were higher in those without antibodies. Specific B cell subsets, anti-PvVir14 circulating antibodies, and NKT cell levels declined after treatment of P. vivax. This study provides the immunological characterization of PvVir14, a unique P. vivax protein, and possible association with acute host's immune responses, providing new information of specific host-parasite interaction. Trial registration: TrialClinicalTrials.gov Identifier: NCT00663546 & ClinicalTrials.gov NCT02334462.
| S-EPMC10115285 | biostudies-literature
Project description:Plasmodium vivax variant interspersed repeats (vir) refer to the key protein used for escaping the host immune system. Knowledge in the genetic variation of vir genes can be used for the development of vaccines or diagnostic methods. Therefore, we evaluated the genetic diversity of the vir genes of P. vivax populations of several Asian countries, including Pakistan, which is a malaria-endemic country experiencing a significant rise in malaria cases in recent years. We analyzed the genetic diversity and population structure of 4 vir genes (vir 4, vir 12, vir 21, and vir 27) in the Pakistan P. vivax population and compared these features to those of the corresponding vir genes in other Asian countries. In Pakistan, vir 4 (S=198, H=9, Hd=0.889, Tajima's D value=1.12321) was the most genetically heterogenous, while the features of vir 21 (S=8, H=7, Hd=0.664, Tajima's D value =-0.63763) and vir 27 (S =25, H =11, Hd =0.682, Tajima's D value=-2.10836) were relatively conserved. Additionally, vir 4 was the most genetically diverse among Asian P. vivax populations, although within population diversity was low. Meanwhile, vir 21 and vir 27 among all Asian populations were closely related genetically. Our findings on the genetic diversity of vir genes and its relationships between populations in diverse geographical locations contribute toward a better understanding of the genetic characteristics of vir. The high level of genetic diversity of vir 4 suggests that this gene can be a useful genetic marker for understanding the P. vivax population structure. Longitudinal genetic diversity studies of vir genes in P. vivax isolates obtained from more diverse geographical areas are needed to better understand the function of vir genes and their use for the development of malaria control measures, such as vaccines.
| S-EPMC11366537 | biostudies-literature
Project description:The vir genes are antigenic genes and are considered to be possible vaccine targets. Since India is highly endemic to Plasmodium vivax, we sequenced 5 different vir genes and investigated DNA sequence variations in 93 single-clonal P. vivax isolates. High variability was observed in all the 5 vir genes; the vir 1/9 gene was highly diverged across Indian populations. The patterns of genetic diversity do not follow geographical locations, as geographically distant populations were found to be genetically similar. The results in general present complex genetic diversity patterns in India, requiring further in-depth population genetic and functional studies.
| S-EPMC4210742 | biostudies-literature
Project description:BackgroundChloroquine has been administered to the soldiers of the Republic of Korea as prophylaxis against vivax malaria. Recent increase in the number of chloroquine-resistant parasites has raised concern over the chemoprophylaxis and treatment of vivax malaria.MethodsTo monitor the development of chloroquine-resistant parasites in the Republic of Korea, analyses of single nucleotide polymorphisms (SNPs) of pvmdr1 and microsatellite markers were performed using samples collected from 55 South Korean soldiers infected with Plasmodium vivax.ResultsFour SNPs, F1076L, T529, E1233, and S1358, were identified. Among these, S1358 was detected for the first time in Korea. The microsatellite-based study revealed higher genetic diversity in samples collected in 2012 than in 2011.ConclusionsTaken together, the results indicate that P. vivax with a newly identified SNP of pvmdr1 has been introduced into the Korean P. vivax population. Therefore, continuous monitoring for chloroquine-resistant parasites is required for controlling vivax malaria in the Republic of Korea.
| S-EPMC4559299 | biostudies-literature