scholarly journals Natural infections with different Plasmodium species induce antibodies reactive to a chimeric Plasmodium vivax recombinant protein

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jessica N. McCaffery ◽  
Balwan Singh ◽  
Douglas Nace ◽  
Alberto Moreno ◽  
Venkatachalam Udhayakumar ◽  
...  

Abstract Background As malaria incidence and transmission in a region decreases, it becomes increasingly difficult to identify areas of active transmission. Improved methods for identifying and monitoring foci of active malaria transmission are needed in areas of low parasite prevalence in order to achieve malaria elimination. Serological assays can provide population-level infection history to inform elimination campaigns. Methods A bead-based multiplex antibody detection assay was used to evaluate a chimeric Plasmodium vivax MSP1 protein (PvRMC-MSP1), designed to be broadly immunogenic for use in vaccine studies, to act as a pan-malaria serological tool based on its ability to capture IgG in plasma samples obtained from naturally exposed individuals. Samples from 236 US travellers with PCR confirmed infection status from all four major Plasmodium species infecting humans, Plasmodium falciparum (n = 181), Plasmodium vivax (n = 38), Plasmodium malariae (n = 4), and Plasmodium ovale (n = 13) were tested for IgG capture using PvRMC-MSP1 as well as the four recombinant MSP1-19 kD isoforms representative of these Plasmodium species. Results Regardless of infecting Plasmodium species, a large proportion of plasma samples from infected US travellers provided a high assay signal to the PvRMC-MSP1 chimeric protein, with 115 high responders out of 236 samples assessed (48.7%). When grouped by active infection, 38.7% P. falciparum-, 92.1% of P. vivax-, 75.0% P. malariae-, and 53.4% of P. ovale-infected individuals displayed high assay signals in response to PvRMC-MSP1. It was also determined that plasma from P. vivax-infected individuals produced increased assay signals in response to the PvRMC-MSP1 chimera as compared to the recombinant PvMSP1 for 89.5% (34 out of 38) of individuals. PvRMC-MSP1 also showed improved ability to capture IgG antibodies from P. falciparum-infected individuals when compared to the capture by recombinant PvMSP1, with high assay signals observed for 38.7% of P. falciparum-infected travellers in response to PvRMC-MSP1 IgG capture compared to just 1.1% who were high responders to capture by the recombinant PvMSP1 protein. Conclusions These results support further study of designed antigens as an approach for increasing sensitivity or broadening binding capacity to improve existing serological tools for determining population-level exposure to Plasmodium species. Including both broad-reacting and Plasmodium species-specific antigen-coated beads in an assay panel could provide a nuanced view of population-level exposure histories, an extensive IgG profile, and detailed seroestimates. A more sensitive serological tool for detection of P. vivax exposure would aid malaria elimination campaigns in co-endemic areas and regions where P. vivax is the dominant parasite.

2020 ◽  
Author(s):  
Jessica N McCaffery ◽  
Balwan Singh ◽  
Douglas Nace ◽  
Alberto Moreno ◽  
Venkatachalam Udhayakumar ◽  
...  

Abstract Background: As malaria incidence and transmission in a region decreases, it becomes increasingly difficult to identify areas of active transmission. Improved methods for identifying and monitoring foci of active malaria transmission are needed in areas of low parasite prevalence in order to achieve malaria elimination. Serological assays can provide population-level infection history to inform elimination campaigns.Methods: A bead-based multiplex antibody detection assay was used to evaluate a chimeric P. vivax MSP1 protein (PvRMC-MSP1), designed to be broadly immunogenic for use in vaccine studies, to act as a pan-malaria serological tool based on its ability to capture IgG in plasma samples obtained from naturally exposed individuals. Samples from 236 US travelers with PCR confirmed infection status from all four major Plasmodium species infecting humans, P. falciparum, P. vivax, P. malariae, and P. ovale were tested for IgG capture using PvRMC-MSP1 as well as the four recombinant MSP1-19 kD isoforms representative of these Plasmodium species.Results: Regardless of infecting Plasmodium species, a majority of plasma samples from infected US travelers provided a high assay signal to the PvRMC-MSP1 chimeric protein. Most individuals that responded to the PmMSP1 or PoMSP1 antigen also responded to PvRMC-MSP1, with very few individuals responding to PmMSP1 or PoMSP1 antigens alone. When grouped by active infection, we observed that plasma from P. vivax-infected individuals produced increased assay signals in response to the PvRMC-MSP1 chimera as compared to the recombinant PvMSP1 for 89.5% (34/38) of individuals. PvRMC-MSP1 also showed improved ability to capture IgG antibodies from P. falciparum-infected individuals when compared to the capture by recombinant PvMSP1. Conclusions: These results support further study of designed antigens as an approach for increasing sensitivity or broadening binding capacity to improve existing serological tools for determining population-level exposure to Plasmodium species. Including both broad-reacting and Plasmodium species-specific antigen-coated beads in an assay panel could provide a nuanced view of population-level exposure histories, an extensive IgG profile, and detailed seroestimates. A more sensitive serological tool for detection of P. vivax exposure would aid malaria elimination campaigns in co-endemic areas and regions where P. vivax is the dominant parasite.


2020 ◽  
Vol 14 (12) ◽  
pp. e0008962
Author(s):  
Lucas E. Buyon ◽  
Ana Maria Santamaria ◽  
Angela M. Early ◽  
Mario Quijada ◽  
Itza Barahona ◽  
...  

Malaria incidence in Panama has plateaued in recent years in spite of elimination efforts, with almost all cases caused by Plasmodium vivax. Notwithstanding, overall malaria prevalence remains low (fewer than 1 case per 1000 persons). We used selective whole genome amplification to sequence 59 P. vivax samples from Panama. The P. vivax samples were collected from two periods (2007–2009 and 2017–2019) to study the population structure and transmission dynamics of the parasite. Imported cases resulting from increased levels of human migration could threaten malaria elimination prospects, and four of the samples evaluated came from individuals with travel history. We explored patterns of recent common ancestry among the samples and observed that a highly genetically related lineage (termed CL1) was dominant among the samples (47 out of 59 samples with good sequencing coverage), spanning the entire period of the collection (2007–2019) and all regions of the country. We also found a second, smaller clonal lineage (termed CL2) of four parasites collected between 2017 and 2019. To explore the regional context of Panamanian P. vivax we conducted principal components analysis and constructed a neighbor-joining tree using these samples and samples collected worldwide from a previous study. Three of the four samples with travel history clustered with samples collected from their suspected country of origin (consistent with importation), while one appears to have been a result of local transmission. The small number of Panamanian P. vivax samples not belonging to either CL1 or CL2 clustered with samples collected from Colombia, suggesting they represent the genetically similar ancestral P. vivax population in Panama or were recently imported from Colombia. The low diversity we observe in Panama indicates that this parasite population has been previously subject to a severe bottleneck and may be eligible for elimination. Additionally, while we confirmed that P. vivax is imported to Panama from diverse geographic locations, the lack of impact from imported cases on the overall parasite population genomic profile suggests that onward transmission from such cases is limited and that imported cases may not presently pose a major barrier to elimination.


2019 ◽  
Vol 18 (1) ◽  
pp. 25
Author(s):  
Aja Fatimah Zohra ◽  
Samsul Anwar ◽  
Aida Fitri ◽  
Muhammad Haikal Nasution

Latar belakang: Malaria merupakan salah satu kasus penyakit yang tidak pernah hilang. World Health Organization (WHO) memperkirakan sebanyak 300 hingga 500 juta orang terinfeksi malaria tiap tahunnya dengan angka kematian berkisar antara 1,5 hingga 2,7 juta pertahun. Pemerintah melalui Rencana Pembangunan Jangka Menengah Nasional (RPJMN) tahun 2015-2019 menargetkan sebanyak 300 kabupaten/kota akan memiliki sertifikasi eliminasi malaria pada tahun 2019. Penelitian ini merupakan penelitian pendahuluan terkait dengan distribusi dan prevalensi kejadian malaria di Provinsi Aceh. Meskipun sebagian besar kabupaten/kota di Provinsi Aceh sudah memiliki sertifikat eliminasi malaria, akan tetapi sebagian wilayah masih terdapat kasus malaria yang relatif tinggi. Penelitian ini bertujuan untuk mengetahui jenis parasit plasmodium yang paling dominan menyebabkan penyakit malaria dan mengklasifikasikan wilayah Provinsi Aceh yang rentan terserang kasus malaria berdasarkan indikator Annual Parasite Incidence (API).Metode: Penelitian ini adalah penelitian analitik kuantitatif dengan pendekatan data panel. Sampel pada penelitian ini adalah kasus malaria yang terjadi di 23 kabupaten/kota di Provinsi Aceh dari tahun 2015 sampai 2018 yang bersumber dari Dinas Kesehatan Provinsi Aceh. Metode statistik yang digunakan adalah analisis non-parametrik Kruskal-Wallis test, Mann-Whitney test dan K-Means Clustering. Hasil: Terdapat tiga jenis parasit yang paling dominan menyebabkan kasus malaria di Provinsi Aceh yaitu plasmodium vivax, plasmodium falcifarum dan plasmodium knowlesi. Berdasarkan indikator Annual Parasite Incidence (API), metode K-means clustering menunjukkan bahwa Kabupaten Aceh Jaya, Kota Sabang dan Kabupaten Aceh Selatan merupakan tiga wilayah yang paling rentan untuk terserang kasus malaria di Provinsi Aceh.Simpulan: Jenis-jenis parasit penyebab kasus malaria tertinggi adalah plasmodium vivax, plasmodium falcifarum dan plasmodium knowlesi. Tiga wilayah di Provinsi Aceh yang paling rentan terserang kasus malaria berdasarkan indikator API adalah Kabupaten Aceh Jaya, Kota Sabang dan Kabupaten Aceh Selatan.ABSTRACTTitle: Classification of Aceh Province Region Based on Vulnerability Levels of Malaria Cases in 2015 - 2018Background: Malaria is a case of an emerging disease. World Health Organization (WHO) estimates that 300 to 500 million people are infected with malaria each year with mortality rate ranging from 1.5 to 2.7 million per year. The government through the National Medium Term Development Plan (RPJMN) for 2015-2019 targets as many as 300 districts/cities to have certification of malaria elimination in 2019. This is a preliminary study related to the distribution and prevalence of malaria incidence in Aceh Province. Although most districts/cities in Aceh Province have been awarded malaria elimination certificates, some regions still have relatively high cases of malaria. This study aims to determine the type of plasmodium parasite that is the most dominant cause of malaria and to classify the regions in Aceh Province that is vulnerable to malaria cases based on the Annual Parasite Incidence (API) indicator.Method: This study is a quantitative analytical research study with panel data approach. The sample in this study was malaria cases that occurred in 23 districts/cities in Aceh Province from 2015 to 2018 obtained from the Aceh Provincial Health Office. The statistical methods used in this study were the non-parametric Kruskal-Wallis test, Mann-Whitney test and K-Means Clustering analyses.Result: There are three types of parasites which are the most dominant causes of malaria cases in Aceh Province, namely plasmodium vivax, plasmodium falcifarum and plasmodium knowlesi. Based on the Annual Parasite Incidence (API) indicator, the K-means clustering method shows that Aceh Jaya District, Sabang City and South Aceh District are the three most vulnerable areas for malaria in Aceh Province.Conclusion: The types of parasites that cause the highest malaria cases are plasmodium vivax, plasmodium falcifarum and plasmodium knowlesi. Three regions in Aceh Province that are most vulnerable to malaria cases based on API indicator are Aceh Jaya District, Sabang City and South Aceh District.


2016 ◽  
Vol 113 (50) ◽  
pp. E8096-E8105 ◽  
Author(s):  
Christian M. Parobek ◽  
Jessica T. Lin ◽  
David L. Saunders ◽  
Eric J. Barnett ◽  
Chanthap Lon ◽  
...  

Cambodia, in which both Plasmodium vivax and Plasmodium falciparum are endemic, has been the focus of numerous malaria-control interventions, resulting in a marked decline in overall malaria incidence. Despite this decline, the number of P. vivax cases has actually increased. To understand better the factors underlying this resilience, we compared the genetic responses of the two species to recent selective pressures. We sequenced and studied the genomes of 70 P. vivax and 80 P. falciparum isolates collected between 2009 and 2013. We found that although P. falciparum has undergone population fracturing, the coendemic P. vivax population has grown undisrupted, resulting in a larger effective population size, no discernable population structure, and frequent multiclonal infections. Signatures of selection suggest recent, species-specific evolutionary differences. Particularly, in contrast to P. falciparum, P. vivax transcription factors, chromatin modifiers, and histone deacetylases have undergone strong directional selection, including a particularly strong selective sweep at an AP2 transcription factor. Together, our findings point to different population-level adaptive mechanisms used by P. vivax and P. falciparum parasites. Although population substructuring in P. falciparum has resulted in clonal outgrowths of resistant parasites, P. vivax may use a nuanced transcriptional regulatory approach to population maintenance, enabling it to preserve a larger, more diverse population better suited to facing selective threats. We conclude that transcriptional control may underlie P. vivax’s resilience to malaria control measures. Novel strategies to target such processes are likely required to eradicate P. vivax and achieve malaria elimination.


PLoS Medicine ◽  
2021 ◽  
Vol 18 (4) ◽  
pp. e1003535
Author(s):  
Narimane Nekkab ◽  
Raquel Lana ◽  
Marcus Lacerda ◽  
Thomas Obadia ◽  
André Siqueira ◽  
...  

Background Despite recent intensification of control measures, Plasmodium vivax poses a major challenge for malaria elimination efforts. Liver-stage hypnozoite parasites that cause relapsing infections can be cleared with primaquine; however, poor treatment adherence undermines drug effectiveness. Tafenoquine, a new single-dose treatment, offers an alternative option for preventing relapses and reducing transmission. In 2018, over 237,000 cases of malaria were reported to the Brazilian health system, of which 91.5% were due to P. vivax. Methods and findings We evaluated the impact of introducing tafenoquine into case management practices on population-level transmission dynamics using a mathematical model of P. vivax transmission. The model was calibrated to reflect the transmission dynamics of P. vivax endemic settings in Brazil in 2018, informed by nationwide malaria case reporting data. Parameters for treatment pathways with chloroquine, primaquine, and tafenoquine with glucose-6-phosphate dehydrogenase deficiency (G6PDd) testing were informed by clinical trial data and the literature. We assumed 71.3% efficacy for primaquine and tafenoquine, a 66.7% adherence rate to the 7-day primaquine regimen, a mean 5.5% G6PDd prevalence, and 8.1% low metaboliser prevalence. The introduction of tafenoquine is predicted to improve effective hypnozoite clearance among P. vivax cases and reduce population-level transmission over time, with heterogeneous levels of impact across different transmission settings. According to the model, while achieving elimination in only few settings in Brazil, tafenoquine rollout in 2021 is estimated to improve the mean effective radical cure rate from 42% (95% uncertainty interval [UI] 41%–44%) to 62% (95% UI 54%–68%) among clinical cases, leading to a predicted 38% (95% UI 7%–99%) reduction in transmission and over 214,000 cumulative averted cases between 2021 and 2025. Higher impact is predicted in settings with low transmission, low pre-existing primaquine adherence, and a high proportion of cases in working-aged males. High-transmission settings with a high proportion of cases in children would benefit from a safe high-efficacy tafenoquine dose for children. Our methodological limitations include not accounting for the role of imported cases from outside the transmission setting, relying on reported clinical cases as a measurement of community-level transmission, and implementing treatment efficacy as a binary condition. Conclusions In our modelling study, we predicted that, provided there is concurrent rollout of G6PDd diagnostics, tafenoquine has the potential to reduce P. vivax transmission by improving effective radical cure through increased adherence and increased protection from new infections. While tafenoquine alone may not be sufficient for P. vivax elimination, its introduction will improve case management, prevent a substantial number of cases, and bring countries closer to achieving malaria elimination goals.


2018 ◽  
pp. S367-S375 ◽  
Author(s):  
Z. RIEDELOVÁ ◽  
P. MÁJEK ◽  
K. PEČÁNKOVÁ ◽  
J. KUČEROVÁ ◽  
F. SURMAN ◽  
...  

Early diagnosis of ongoing malignant disease is crucial to improve survival rate and life quality of the patients and requires sensitive detection of specific biomarkers e.g. prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), etc. In spite of current technological advances, malignant diseases are still identified in rather late stages, which have detrimental effect on the prognosis and treatment of the disease. Here, we present a biosensor able to detect fetuin-A, a potential multibiomarker. The biosensing platform is based on polymer brush combining antifouling monomer units of N-(2-hydroxypropyl)methacrylamide (HPMA) and carboxybetaine methacrylamide (CBMAA), statistically copolymerized by surface-initiated atom transfer radical polymerization. The copolymer poly(HPMA-co-CBMAA) exhibits excellent non-fouling properties in the most relevant biological media (i.e. blood plasma) as well as antithrombogenic surface properties by preventing the adhesion of blood components (i.e. leukocytes; platelets; and erythrocytes). Moreover, the polymer brush can be easily functionalized with biorecognition elements maintaining high resistance to blood fouling and the binding capacity can be regulated by tuning the ratio between CBMAA and HPMA units. The superior antifouling properties of the copolymer even after biofunctionalization were exploited to fabricate a new plasmonic biosensor for the analysis of fetuin-A in real clinical blood plasma samples. The assay used in this work can be explored as label-free affinity biosensor for diagnostics of different biomarkers in real clinical plasma samples and to shift the early biomarker detection toward novel biosensor technologies allowing point of care analysis.


Author(s):  
Rhea Longley ◽  
Michael White ◽  
Jessica Brewster ◽  
Zoe Liu ◽  
Caitlin Bourke ◽  
...  

To achieve malaria elimination, new tools are required to explicitly target Plasmodium vivax. Recently, a novel panel of P. vivax proteins were identified and validated as serological markers for detecting recent exposure to P. vivax within the last 9 months. In order to improve the sensitivity and specificity of these markers, IgM in addition to IgG antibody responses were assessed to a down-selected panel of 20 P. vivax proteins. IgM was tested using archival plasma samples from observational cohort studies conducted in malaria-endemic regions of Thailand and Brazil. IgM responses to these proteins generally had poorer classification performance than IgG.


2020 ◽  
Author(s):  
Yuling Li ◽  
Yubing Hu ◽  
Yan Zhao ◽  
Qinghui Wang ◽  
Huguette Gaelle Ngassa Mbenda ◽  
...  

Abstract Background Countries within the Greater Mekong Sub-region (GMS) of Southeast Asia have committed to eliminating malaria by 2030. Although the malaria situation has greatly improved, malaria transmission remains at international border regions. In some areas, Plasmodium vivax has become the predominant parasite. To gain a better understanding of transmission dynamics, knowledge on the changes of P. vivax populations after the scale-up of control interventions will guide more effective targeted control efforts. Methods This study investigated genetic diversity and population structures in 206 P. vivax clinical samples collected at two time points in two international border areas: the China-Myanmar border (CMB) (n=50 in 2004 and n=52 in 2016) and Thailand-Myanmar border (TMB) (n=50 in 2012 and n=54 in 2015). Parasites were genotyped using 10 microsatellite markers. Results Despite intensified control efforts, genetic diversity remained high ( H E = 0.66-0.86) and was not significantly different among the four populations ( P >0.05). Specifically, H E slightly decreased from 0.76 in 2004 to 0.66 in 2016 at the CMB and increased from 0.80 in 2012 to 0.86 in 2015 at the TMB. The proportions of polyclonal infections varied significantly among the four populations ( P < 0.05), and showed substantial decreases from 48.0% in 2004 to 23.7 at the CMB and from 40.0% in 2012 to 30.7% in 2015 at the TMB, with corresponding decreases in the multiplicity of infection. Consistent with the continuous decline of malaria incidence in the GMS over time, there were also increases in multilocus linkage disequilibrium, suggesting more fragmented and increasingly inbred parasite populations. There were considerable genetic differentiation and sub-division among the four tested populations. Temporal genetic differentiation was observed at each site ( F ST = 0.081 at the CMB and F ST = 0.133 at the TMB). Various degrees of clustering were evident between the older parasite samples collected in 2004 at the CMB with the 2016 CMB and 2012 TMB populations, suggesting some of these parasites had shared ancestry. In contrast, the 2015 TMB population was genetically distinctive, which may reflect a process of population replacement. Whereas the effective population size ( N e ) at the CMB showed a decrease from 4979 in 2004 to 3052 in 2016 with the infinite allele model, the N e at the TMB experienced an increase from 6289 to 10259. Conclusions With enhanced control efforts on malaria, P. vivax at the TMB and CMB showed considerable spatial and temporal differentiation, but the presence of large P. vivax reservoirs still sustained genetic diversity and transmission. These findings provide new insights into P. vivax transmission dynamics and population structure in these border areas of the GMS. Coordinated and integrated control efforts on both sides of international borders are essential to reach the goal of regional malaria elimination.


Author(s):  
Rhea J Longley ◽  
Michael T White ◽  
Jessica Brewster ◽  
Zoe S J Liu ◽  
Caitlin Bourke ◽  
...  

Abstract To achieve malaria elimination, new tools are required to explicitly target Plasmodium vivax. Recently, a novel panel of P. vivax proteins were identified and validated as serological markers for detecting recent exposure to P. vivax within the last 9 months. In order to improve the sensitivity and specificity of these markers, IgM in addition to IgG antibody responses were assessed to a down-selected panel of 20 P. vivax proteins. IgM was tested using archival plasma samples from observational cohort studies conducted in malaria-endemic regions of Thailand and Brazil. IgM responses to these proteins generally had poorer classification performance than IgG.


1972 ◽  
Vol 69 (3) ◽  
pp. 517-525 ◽  
Author(s):  
T. Uozumi ◽  
H. Manabe ◽  
Y. Kawashima ◽  
Y. Hamanaka ◽  
Y. Monden ◽  
...  

ABSTRACT The response of plasma cortisol, corticosterone and non-protein-bound cortisol in the extracorporeal circulation was investigated in 14 patients. The pre-perfusion levels of plasma cortisol, corticosterone and non-protein-bound cortisol were significantly elevated. During and immediately after perfusion, the levels of cortisol and corticosterone were found to decrease significantly from the pre-perfusion levels, while the percentage of non-protein-bound cortisol was shown to increase significantly. This indicates a marked decrease in cortisol binding capacity of plasma during extracorporeal circulation. Moreover in 200 plasma samples, it was demonstrated that the cortisol level increased markedly and the cortisol binding capacity decreased slightly during and shortly after major surgery without perfusion. It is concluded that stressful situations in major surgery with or without perfusion are associated with markedly increased levels of biologically active non-protein-bound cortisol. The elevated level of non-protein-bound cortisol in surgery seems to be dependent on the increase in the level of plasma cortisol as well as on the decrease in the cortisol binding capacity of plasma. Although the increased plasma cortisol plays the most important role in surgery with no perfusion, the decreased cortisol binding capacity may be the more effective factor involved during perfusion.


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