scholarly journals Natural Infections With Different Plasmodium Species Induce Antibodies Reactive to A Chimeric Plasmodium Vivax Recombinant Protein

2020 ◽  
Author(s):  
Jessica N McCaffery ◽  
Balwan Singh ◽  
Douglas Nace ◽  
Alberto Moreno ◽  
Venkatachalam Udhayakumar ◽  
...  
Keyword(s):  
Malaria Elimination ◽  
Malaria Incidence ◽  
Binding Capacity ◽  
Specific Antigen ◽  
Plasmodium Species ◽  
Chimeric Protein ◽  
Population Level ◽  
Parasite Prevalence ◽  
Antibody Detection ◽  
Plasma Samples

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.

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 ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Malaria Elimination ◽  
Malaria Incidence ◽  
Binding Capacity ◽  
Specific Antigen ◽  
Plasmodium Species ◽  
Population Level ◽  
Antibody Detection ◽  
Plasma Samples ◽  
High Responders

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.

scholarly journals SPR Biosensor for Quantification of Fetuin-A as a Promising Multibiomarker

2018 ◽  
pp. S367-S375 ◽  
Author(s):  
Z. RIEDELOVÁ ◽  
P. MÁJEK ◽  
K. PEČÁNKOVÁ ◽  
J. KUČEROVÁ ◽  
F. SURMAN ◽  
...  
Keyword(s):  
Blood Plasma ◽  
Binding Capacity ◽  
Point Of Care ◽  
Specific Antigen ◽  
Polymer Brush ◽  
Life Quality ◽  
Plasma Samples ◽  
Label Free ◽  
Fetuin A ◽  
Technological Advances

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.

scholarly journals Malaria Elimination: The Role and Value of Sero-Surveillance

2021 ◽  
Author(s):  
Kingsley Badu ◽  
Amma Aboagyewa Larbi ◽  
Kwadwo Boampong
Keyword(s):  
Malaria Transmission ◽  
Malaria Elimination ◽  
Diagnostic Testing ◽  
Plasmodium Species ◽  
Parasite Prevalence ◽  
Molecular Testing ◽  
Direct Function ◽  
Individual Level ◽  
Western Africa ◽  
Parasite Exposure

As countries move from intense malaria transmission to low transmission there will be a demand for more sensitive tools and approaches in tracking malaria transmission dynamics. Surveillance tools that are sensitive in tracking real time infectious bites as well as infectious reservoir will be preferred to counting number of cases in the hospital or parasite prevalence. The acquisition and maintenance of anti-malarial antibodies is a direct function of parasite exposure, seroprevalence rates has been used as an efficient tool in assessing malaria endemicity and confirming malaria elimination. Plasmodium antibodies are explicit biomarkers that can be utilised to track parasite exposure over more extensive time spans than microscopy, rapid diagnostic testing or molecular testing and the conventional entomological inoculation rate. Seroprevalence studies can therefore help monitor the impact of malaria control interventions, especially when the parasite occurrence is low. As a result, antibody responses to Anopheles salivary proteins or Plasmodium species may potentially offer reliable information of recent or past exposure; recognise short-term or gradual changes in exposure to Plasmodium infection or to estimate individual-level exposure to infection. This book chapter will present about four studies we have conducted across eastern and western Africa on the efficiency of salivary gland proteins and antimalarial antibodies in tracking malaria transmission intensity. We hope that these could be used as surveillance tools in malaria elimination efforts.

PLASMA CORTISOL, CORTICOSTERONE AND NON-PROTEIN-BOUND CORTISOL IN EXTRACORPOREAL CIRCULATION

1972 ◽  
Vol 69 (3) ◽  
pp. 517-525 ◽  
Author(s):  
T. Uozumi ◽  
H. Manabe ◽  
Y. Kawashima ◽  
Y. Hamanaka ◽  
Y. Monden ◽  
...  
Keyword(s):  
Cortisol Level ◽  
Extracorporeal Circulation ◽  
Plasma Cortisol ◽  
Elevated Level ◽  
Marked Decrease ◽  
Binding Capacity ◽  
Biologically Active ◽  
Major Surgery ◽  
Plasma Samples ◽  
Effective Factor

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.

Spatiotemporal distributed lag modelling of multiple Plasmodium species in a malaria elimination setting

2021 ◽  
Vol 30 (1) ◽  
pp. 22-34
Author(s):  
Chawarat Rotejanaprasert ◽  
Duncan Lee ◽  
Nattwut Ekapirat ◽  
Prayuth Sudathip ◽  
Richard J Maude
Keyword(s):  
Data Streams ◽  
Malaria Elimination ◽  
Parasite Species ◽  
Climatic Factors ◽  
Plasmodium Species ◽  
Clinical Malaria ◽  
Spatiotemporal Patterns ◽  
Distributed Lag ◽  
Multiple Data

In much of the Greater Mekong Sub-region, malaria is now confined to patches and small foci of transmission. Malaria transmission is seasonal with the spatiotemporal patterns being associated with variation in environmental and climatic factors. However, the possible effect at different lag periods between meteorological variables and clinical malaria has not been well studied in the region. Thus, in this study we developed distributed lagged modelling accounting for spatiotemporal excessive zero cases in a malaria elimination setting. A multivariate framework was also extended to incorporate multiple data streams and investigate the spatiotemporal patterns from multiple parasite species via their lagged association with climatic variables. A simulation study was conducted to examine robustness of the methodology and a case study is provided of weekly data of clinical malaria cases at sub-district level in Thailand.

ENZYMATISCH-FLUOROMETRISCHE BESTIMMUNG DER CORTISOLBINDUNGSKAPAZITÄT DES PLASMA

1967 ◽  
Vol 56 (1) ◽  
pp. 99-106 ◽  
Author(s):  
K. Leybold ◽  
J. Rieper ◽  
L. Weissbecker
Keyword(s):  
Binding Capacity ◽  
Liver Microsomes ◽  
Mean Value ◽  
Female Rats ◽  
Plasma Samples ◽  
Simple Method ◽  
Adult Men ◽  
The Mean ◽  
Precision And Accuracy

ABSTRACT A simple method for the determination of cortisol-binding capacity is described. For saturation of the cortisol-binding proteins, plasma samples are incubated with an excess of cortisol. In the next step NADPH and liver microsomes of female rats are added. The microsomal Δ4-3-ketosteroid hydrogenase only reduces non protein-bound cortisol to tetrahydrocortisol-5α. Then the steroids are extracted by dichloromethane, and after some purification steps analyzed by fluorometry. Tetrahydrocortisol gives practically no fluorescence. The cortisol determined by this method corresponds to protein-bound cortisol and indicates the extent of cortisolbinding capacity. Precision and accuracy of the method were found to be good. The values of cortisol-binding capacity obtained by our method are compared with the results of other authors. The mean value of adult men was 25.5 ± 3.4 μg/100 ml, that of pregnant women, mens IX-X, 42.3 ± 4.2 μg/100 ml.

scholarly journals Development of Antibody Detection ELISA Based on Immunoreactive Toxins and Toxin-Derived Peptides to Evaluate the Neutralization Potency of Equine Plasma against Naja atra in Taiwan

Toxins ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 818
Author(s):  
Chien-Chun Liu ◽  
Yung-Chin Hsiao ◽  
Lichieh Julie Chu ◽  
Po-Jung Wang ◽  
Chien-Hsin Liu ◽  
...  
Keyword(s):  
Antibody Titer ◽  
Large Scale ◽  
Antibody Detection ◽  
Major Protein ◽  
Plasma Samples ◽  
In Vivo Assay ◽  
Equine Plasma ◽  
Freeze Dried ◽  
Naja Atra

Naja atra, also known as Taiwanese cobra, is one of the most prevalent venomous snakes in Taiwan. Clinically, freeze-dried neurotoxic antivenom (FNAV) produced from horses by Taiwan Centers for Disease Control (CDC) has been the only approved treatment for N. atra envenoming for the last few decades. During antivenom production, large numbers of mice are used in the in vivo assay to determine whether the neutralization potency of hyperimmunized equines is satisfactory for large-scale harvesting. However, this in vivo assay is extremely laborious, expensive, and significantly impairs animal welfare. In the present study, we aimed to develop an in vitro ELISA-based system that could serve as an alternative assay to evaluate the neutralization potency of plasma from hyperimmunized equines. We initially obtained 51 plasma samples with known (high or low) neutralization potency assessed in vivo from 9 hyperimmunized equines and subsequently determined their antibody titers against the five major protein components of N. atra venom (neurotoxin (NTX), phospholipase A2 (PLA2), cytotoxin (CTX), cysteine-rich secretory protein (CRISP), and snake venom metalloproteinase (SVMP)) via ELISA. The antibody titer against NTX was the most effective in discriminating between high and low potency plasma samples. To identify the specific epitope(s) of NTX recognized by neutralization potency-related antibodies, 17 consecutive NTX-derived pentadecapeptides were synthesized and used as antigens to probe the 51 equine plasma samples. Among the 17 peptides, immunoreactive signals for three consecutive peptides (NTX1-8, NTX1-9, and NTX1-10) were significantly higher in the high potency relative to low potency equine plasma groups (p < 0.0001). Our ELISA system based on NTX1-10 peptide (RWRDHRGYRTERGCG) encompassing residues 28–42 of NTX displayed optimal sensitivity (96.88%) and specificity (89.47%) for differentiating between high- and low-potency plasma samples (area under the receiver operating characteristic curve (AUC) = 0.95). The collective data clearly indicate that the antibody titer against NTX protein or derived peptides can be used to efficiently discriminate between high and low neutralization potency of plasma samples from venom-immunized horses. This newly developed antibody detection ELISA based on NTX or its peptide derivatives has good potential to complement or replace the in vivo rodent assay for determining whether the neutralization potency of equine plasma is satisfactory for large-scale harvesting in the antivenom production process against N. atra.

scholarly journals Micro-Stratification for Malaria Transmission Risk in a High Burden Area of Honduras

2021 ◽  
Author(s):  
José Orlinder Nicolas ◽  
Denis Escobar ◽  
Engels Banegas ◽  
José Ramón Valdez ◽  
Rosa Elena Mejía Torres ◽  
...  
Keyword(s):  
Malaria Elimination ◽  
Malaria Incidence ◽  
Epidemiological Data ◽  
Transmission Risk ◽  
Who Guidelines ◽  
Demographic Information ◽  
Health System Improvement ◽  
System Improvement ◽  
Endemic Areas ◽  
Elimination Goal

Abstract Background As Malaria cases are continuously reported across the globe, epidemiological and integral approaches should be considered for an optimal stratification on endemic areas for elimination goal. In Central America, a 75% reduction in malaria incidence has been reported between 2000 and 2015, similarly, in Honduras, more than 75% of total cases in 2016 were concentrated in 7 municipalities, mainly in Gracias Dios department. Achieve malaria elimination in Honduras demands the implementation of strategies to identify main hotspots. Methods Based on WHO guidelines, local malaria epidemiological data from case-based surveillance system of the Ministry of Health between January and December 2016 were analysed. Furthermore, on field evaluations were carried out in Puerto Lempira municipality, Gracias a Dios department to an analysis validation. Finally, a set of epidemiological components were generated and proposed together with risk-factor description and proposed actions for health system improvement. Results On 2016, Gracias a Dios reported 61% of total malaria cases in Honduras; based on our analysis, 12 micro-areas were identified, including epidemiological, entomological, and socio-demographic information from local technicians. Conclusions Malaria elimination in endemic areas urges implementation of different strategies, here we show the on-field micro-stratification process of 12 “micro-areas” carried out in one endemic department of Honduras. This information provides a more targeted strategy for diagnosis, treatment, and vector control interventions for malaria elimination goal in Honduras.

scholarly journals Miniature Single-Particle Immunoassay for Prostate-specific Antigen in Serum Using Recombinant Fab Fragments

2000 ◽  
Vol 46 (11) ◽  
pp. 1755-1761 ◽  
Author(s):  
Harri Härmä ◽  
Piia Tarkkinen ◽  
Tero Soukka ◽  
Timo Lövgren
Keyword(s):  
Prostate Specific Antigen ◽  
Single Particle ◽  
Binding Capacity ◽  
Specific Antigen ◽  
Genetically Engineered ◽  
Covalent Attachment ◽  
Serum Samples ◽  
Fab Fragment ◽  
Fab Fragments ◽  
Total Psa

Abstract Background: Quantitative, miniaturized nucleic acid assays and immunoassays can be developed with single microparticles, microfluorometric detection, and intrinsically fluorescent lanthanide chelates in a multiple assay format to decrease reagent consumption, cost, and assay time. We used recombinant Fab fragments to capture and detect free and total prostate-specific antigen (PSA) from serum in a submicroliter volume single-particle immunoassay. Methods: Genetically engineered thiol-Fab or thiolated monoclonal antibodies (mAbs) were covalently attached onto uniformly sized 60-μm maleimide-activated microparticles. Free and total PSA were detected with europium- or terbium-labeled Fab fragments on a single microparticle using a microfluorometer in a time-resolved mode. Results: The detection limit of the free- and total-PSA assays (mean + 3 SD of zero calibrator) was 0.35 μg/L, with a total volume of 330 nL per particle. An excellent correlation was found in microparticle and microtiter-well assays for 21 serum samples: slopes for free and total PSA were 1.06 ± 0.03 and 1.03 ± 0.02, respectively (Sy|x = 0.084 and 0.057 μg/L), with intercepts of 0.013 ± 0.018 and 0.013 ± 0.017 μg/L (R &gt;0.99). Furthermore, the particle-immobilized Fab fragment had a PSA binding capacity 1.5-fold higher than the intact mAb capacity on a single microparticle. Capacity, kinetics, and sensitivity of the Fab fragment and intact mAb assays in the microparticle and microtiter well formats are discussed. Conclusions: With site-specific (cysteine tail) covalent attachment of Fab fragments on a microparticle, subattomole amounts of PSA can be detected quantitatively.

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