scholarly journals Antibody Activities in Hyperimmune Plasma Against the Rhodococcus equi Virulence -Associated Protein A or Poly-N-Acetyl Glucosamine are Associated with Protection of Foals Against Rhodococcal Pneumonia

2021 ◽  
Author(s):  
Susanne K. Kahn ◽  
Colette Cywes-Bentley ◽  
Glenn P. Blodgett ◽  
Nathan M. Canaday ◽  
Carly E. Turner ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Protein A ◽  
Rhodococcus Equi ◽  
Antibody Activity ◽  
Correlates Of Protection ◽  
Quarter Horse ◽  
Surface Polysaccharide ◽  
Rhodococcal Pneumonia ◽  
Functional Antibodies ◽  
Breeding Farms

The efficacy of transfusion with hyperimmune plasma (HIP) for preventing pneumonia caused by Rhodococcus equi remains ill-defined. Quarter Horse foals at 2 large breeding farms were randomly assigned to be transfused with 2 L of HIP from adult donors hyperimmunized either with R. equi (RE HIP) or a conjugate vaccine eliciting antibody to the surface polysaccharide β-1→6-poly- N -acetyl glucosamine (PNAG HIP) within 24 hours of birth.  Antibody activities against PNAG and the rhodococcal virulence-associated protein A (VapA), and to deposition of complement component 1q (C?1q) onto PNAG were determined by ELISA, and then associated with either clinical pneumonia at Farm A (n=119) or subclinical pneumonia at Farm B (n=114).  Data were analyzed using multivariable logistic regression. Among RE HIP-transfused foals, the odds of pneumonia were approximately 6-fold higher (P = 0.0005) among foals with VapA antibody activity ≤ the population median.  Among PNAG HIP-transfused foals, the odds of pneumonia were approximately 3-fold (P = 0.0347) and 11-fold (P = 0.0034) higher for foals with antibody activities ≤ the population median for PNAG or C?1q deposition, respectively.  Results indicated that levels of activity of antibodies against R. equi antigens are correlates of protection against both subclinical and clinical R. equi pneumonia in field settings. Among PNAG HIP-transfused foals, activity of antibodies with C?1q deposition (an indicator of functional antibodies) were a stronger predictor of protection than PNAG antibody activity alone. Collectively, these findings suggest that the amount and activity of antibodies in HIP ( i.e. , plasma volume and/or antibody activity) is positively associated with protection against R. equi pneumonia in foals.

scholarly journals Antibody activities in hyperimmune plasma against the Rhodococcus equi virulence -associated protein A or poly-N-acetyl glucosamine are associated with protection of foals against rhodococcal pneumonia

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0250133
Author(s):  
Susanne K. Kahn ◽  
Colette Cywes-Bentley ◽  
Glenn P. Blodgett ◽  
Nathan M. Canaday ◽  
Carly E. Turner-Garcia ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Protein A ◽  
Rhodococcus Equi ◽  
Antibody Activity ◽  
Correlates Of Protection ◽  
Quarter Horse ◽  
Surface Polysaccharide ◽  
Rhodococcal Pneumonia ◽  
Functional Antibodies ◽  
Breeding Farms

The efficacy of transfusion with hyperimmune plasma (HIP) for preventing pneumonia caused by Rhodococcus equi remains ill-defined. Quarter Horse foals at 2 large breeding farms were randomly assigned to be transfused with 2 L of HIP from adult donors hyperimmunized either with R. equi (RE HIP) or a conjugate vaccine eliciting antibody to the surface polysaccharide β-1→6-poly-N-acetyl glucosamine (PNAG HIP) within 24 hours of birth. Antibody activities against PNAG and the rhodococcal virulence-associated protein A (VapA), and to deposition of complement component 1q (C՛1q) onto PNAG were determined by ELISA, and then associated with either clinical pneumonia at Farm A (n = 119) or subclinical pneumonia at Farm B (n = 114). Data were analyzed using multivariable logistic regression. Among RE HIP-transfused foals, the odds of pneumonia were approximately 6-fold higher (P = 0.0005) among foals with VapA antibody activity ≤ the population median. Among PNAG HIP-transfused foals, the odds of pneumonia were approximately 3-fold (P = 0.0347) and 11-fold (P = 0.0034) higher for foals with antibody activities ≤ the population median for PNAG or C՛1q deposition, respectively. Results indicated that levels of activity of antibodies against R. equi antigens are correlates of protection against both subclinical and clinical R. equi pneumonia in field settings. Among PNAG HIP-transfused foals, activity of antibodies with C՛1q deposition (an indicator of functional antibodies) were a stronger predictor of protection than was PNAG antibody activity alone. Collectively, these findings suggest that the amount and activity of antibodies in HIP (i.e., plasma volume and/or antibody activity) is positively associated with protection against R. equi pneumonia in foals.

scholarly journals Maternal Pregnancy Associated Plasma Protein-A Levels in Late First Trimester as a Predictor of Miscarriage- A Cross-sectional Study

2021 ◽  
Author(s):  
Nivedita Sinha ◽  
Alpana Singh ◽  
BD Banerjee ◽  
Rachna Agarwal ◽  
Himsweta Srivastva
Keyword(s):  
Logistic Regression ◽  
Sensitivity And Specificity ◽  
Plasma Protein ◽  
Protein A ◽  
Predictive Marker ◽  
First Trimester ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Asymptomatic Women

Indroduction: Miscarriage is the most common complication of pregnancy. Defective implantation is one of the common causes of miscarriage. Pregnancy Associated Plasma Protein-A (PAPP-A) is secreted from syncytiotrophoblast and it enables trophoblast invasion. Few studies have shown association of PAPP-A with miscarriage. However, there is limited data available to establish the role of PAPP-A as a predictive marker of miscarriage, especially in Indian population. Aim: To determine the potential of maternal PAPP-A level estimation in asymptomatic women in late first trimester (10-13 weeks) with viable foetus in predicting subsequent miscarriage. Materials and Methods: This was an observational, cross-sectional study conducted from November 2016 to April 2018 at University College of Medical Science and Guru Teg Bahadur Hospital, Delhi, India. Asymptomatic pregnant women (N=500) at 10-13 weeks of gestation were recruited from an antenatal clinic after confirmation of foetal viability. A 2 mL of blood sample was collected and serum PAPP-A level was measured. Independent t-test and Chi-square test was used to compare continuous data and Mann-Whitney U test was used to compare PAPP-A Multiple of Median (MOM). Logistic regression was used to estimate risk of miscarriage. Results: Out of 500 participants, 9 were lost to follow-up. From remaining N=491, 32 (6.5%) women had a miscarriage. PAPP-A levels were significantly decreased in miscarriage group compared to ongoing pregnancy group with median MOM 0.116 (0.080-0.17) and 1.25 (0.665-3.249) respectively (p-value <0.001). PAPP-A MOM value of ≤10th percentile sensitivity and specificity of detection of miscarriage was 81.25% and 94.98% and at ≤5th percentile sensitivity and specificity was 40.62% and 97.82%, respectively. Lower the percentile cut-off of serum PAPP-A value, higher was the specificity and positive predictive value for prediction of miscarriage. By applying logistic regression we found that if PAPP-A MOM decreases by 1 unit the chances of miscarriage increased by 1.2 times. By this model 63.2% of cases could be explained (Nagelkerke R Square=0.632). For prediction of pregnancies likely to miscarry, the area under Receiver Operator Characteristic (ROC) curve (95% CI) was 0.969 (0.955-0.983). Conclusion: Low serum PAPP-A levels from asymptomatic women in late 1st trimester is a good predictive marker of miscarriage.

Pregnancy-associated plasma protein-a is associated with subclinical atherosclerosis in men with HIV infection

2018 ◽  
Vol 67 (5) ◽  
pp. 821-825
Author(s):  
Suleyman Sezai Yildiz ◽  
Sukru Cetin ◽  
Kudret Keskin ◽  
Alper Gunduz ◽  
Gokhan Cetinkal ◽  
...  
Keyword(s):  
Logistic Regression ◽  
T Cell ◽  
Plasma Protein ◽  
Roc Analysis ◽  
Subclinical Atherosclerosis ◽  
Pearson Correlation ◽  
Protein A ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Asymptomatic Hiv

The pathophysiology of an early and accelerated atherosclerotic process is complex and multifactorial in HIV-infected men compared with HIV-non-infected men. Several biomarkers have been well studied in the detection of the early stage of atherosclerosis, but studies are limited in HIV-infected men. The objective of this study was to investigate the association between serum pregnancy-associated plasma protein-A (PAPP-A) and carotid intima-media wall thickness (CIMT) in asymptomatic HIV-infected men. This a case–control study group comprising 118 HIV-infected men and 60 age-matched and gender-matched HIV-non-infected men. Serum PAPP-A was measured using an ELISA kit and carotid IMT was evaluated by Doppler ultrasonography in all subjects. Statistical analysis included receiver-operating characteristic (ROC) analysis, Pearson correlation and logistic regression analysis. Serum PAPP-A level was significantly higher in HIV +CIMT+ group compared with HIV +CIMT group and HIV–CIMT- group. We found a positive correlation between PAPP-A and increased CIMT (r=0.737, p<0.0001), and a negative correlation between nadir CD4 T cell counts and increased CIMT (r=−0.526, p<0.001). In multivariate logistic regression analyses, PAPP-A, nadir CD4 T cell count and age were significantly associated with subclinical atherosclerosis (p<0.001, p=0.006 and p=0.032, respectively). In ROC analysis, PAPP-A levels of >3.70 µg/mL were associated with subclinical atherosclerosis in HIV+ men with a specificity of 100% and a sensitivity of 71% (area under the curve: 0.949, 95% CI 0.875 to 1.000, p<0.001). Serum PAPP-A level was strongly correlated with increased CIMT in HIV-infected men. PAPP-A might be used as an early biomarker to identify atherosclerosis in asymptomatic HIV-infected men.

Prevalence and risk factors associated with emergence of Rhodococcus equi resistance to macrolides and rifampicin in horse-breeding farms in Kentucky, USA

2019 ◽  
Vol 235 ◽  
pp. 243-247 ◽  
Author(s):  
Laura Huber ◽  
Steeve Giguère ◽  
Noah D. Cohen ◽  
Nathan M. Slovis ◽  
Amanda Hanafi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Rhodococcus Equi ◽  
Factors Associated ◽  
Horse Breeding ◽  
Breeding Farms

scholarly journals Clearance of Virulent but Not Avirulent Rhodococcus equi from the Lungs of Adult Horses Is Associated with Intracytoplasmic Gamma Interferon Production by CD4+ and CD8+ T Lymphocytes

2003 ◽  
Vol 10 (2) ◽  
pp. 208-215 ◽  
Author(s):  
Stephen A. Hines ◽  
Diana M. Stone ◽  
Melissa T. Hines ◽  
Debby C. Alperin ◽  
Donald P. Knowles ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Virulent Strain ◽  
Lavage Fluid ◽  
Rhodococcus Equi ◽  
Gamma Interferon ◽  
Effective Vaccine ◽  
Virulence Plasmid ◽  
Flow Cytometric Method ◽  
Ifn Γ ◽  
Rhodococcal Pneumonia

ABSTRACT Rhodococcus equi is a gram-positive bacterium that infects alveolar macrophages and causes rhodococcal pneumonia in horses and humans. The virulence plasmid of R. equi appears to be required for both pathogenicity in the horse and the induction of protective immunity. An understanding of the mechanisms by which virulent R. equi circumvents protective host responses and by which bacteria are ultimately cleared is important for development of an effective vaccine. Six adult horses were challenged with either virulent R. equi or an avirulent, plasmid-cured derivative. By using a flow cytometric method for intracytoplasmic detection of gamma interferon (IFN-γ) in equine bronchoalveolar lavage fluid (BALF) cells, clearance of the virulent strain was shown to be associated with increased numbers of pulmonary CD4+ and CD8+ T lymphocytes producing IFN-γ. There was no change in IFN-γ-positive cells in peripheral blood, suggesting that a type 1 recall response at the site of challenge was protective. The plasmid-cured strain of R. equi was cleared in horses without a significant increase in IFN-γ-producing T lymphocytes in BALF. In contrast to these data, a previous report in foals suggested an immunomodulating role for R. equi virulence plasmid-encoded products in downregulating IFN-γ expression by equine CD4+ T lymphocytes. Intracytoplasmic detection of IFN-γ provides a method to better determine whether modulation of macrophage-activating cytokines by virulent strains occurs uniquely in neonates and contributes to their susceptibility to rhodococcal pneumonia.

Hematologic and immunophenotypic factors associated with development of Rhodococcus equi pneumonia of foals at equine breeding farms with endemic infection

2004 ◽  
Vol 100 (1-2) ◽  
pp. 33-48 ◽  
Author(s):  
M.Keith Chaffin ◽  
Noah D. Cohen ◽  
Ronald J. Martens ◽  
Ronnie F. Edwards ◽  
Mark Nevill ◽  
...  
Keyword(s):  
Rhodococcus Equi ◽  
Factors Associated ◽  
Breeding Farms

scholarly journals Antibody-based vaccine for tuberculosis: validation in horse foals challenged with the TB-related pathogen Rhodococcus equi

2018 ◽  
Author(s):  
C. Cywes-Bentley ◽  
J. N. Rocha ◽  
A. I. Bordin ◽  
M. Vinacur ◽  
S. Rehman ◽  
...  
Keyword(s):  
Severe Pneumonia ◽  
Surface Expression ◽  
Interferon Γ ◽  
Rhodococcus Equi ◽  
Intracellular Pathogens ◽  
Severe Respiratory Distress ◽  
Antibody Recognition ◽  
Immune Correlates ◽  
Vaccine Antigens ◽  
Surface Polysaccharide

AbstractImmune correlates for protection against Mycobacterium tuberculosis (Mtb) infection and other intracellular pathogens are largely undetermined. Whether there is a role for antibody-mediated immunity is controversial. Rhodococcus equi is an intracellular pathogen causing severe pneumonia in young horse foals, eliciting a disease with many similarities to TB including intracellular residence, formation of granulomas and induction of severe respiratory distress. No purified vaccine antigens exist for R. equi or Mtb infections. Both express the microbial surface polysaccharide antigen poly-N-acetyl glucosamine (PNAG). In a randomized, controlled, blinded challenge trial, vaccination of pregnant mares with a synthetic PNAG oligosaccharide conjugated to tetanus toxoid elicited antibody that transferred to foals via colostrum and provided nearly complete protection against R. equi pneumonia. Infusion of PNAG-hyperimmune plasma protected 100% of foals against R. equi pneumonia. Vaccination induced opsonic antibodies that killed extracellular and intracellular R. equi and other intracellular pathogens. Killing of intracellular organisms was dependent on antibody recognition of surface expression of PNAG on infected macrophages, complement deposition and PMN-assisted lysis of infected macrophages. Protection also correlated with PBMC release of interferon-γ in response to PNAG. Antibody-mediated opsonic killing and interferon-γ release in response to PNAG may protect against disease caused by intracellular bacterial pathogens.

Epidemiology and Molecular Basis of Multidrug Resistance in Rhodococcus equi

2021 ◽  
Vol 85 (2) ◽  
Author(s):  
Sonsiray Álvarez-Narváez ◽  
Laura Huber ◽  
Steeve Giguère ◽  
Kelsey A. Hart ◽  
Roy D. Berghaus ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Animal Health ◽  
Domestic Animals ◽  
Rhodococcus Equi ◽  
Production Costs ◽  
Antimicrobial Use ◽  
Human Beings ◽  
Content Type ◽  
Horse Breeding ◽  
Breeding Farms

SUMMARY The development and spread of antimicrobial resistance are major concerns for human and animal health. The effects of the overuse of antimicrobials in domestic animals on the dissemination of resistant microbes to humans and the environment are of concern worldwide. Rhodococcus equi is an ideal model to illustrate the spread of antimicrobial resistance at the animal-human-environment interface because it is a natural soil saprophyte that is an intracellular zoonotic pathogen that produces severe bronchopneumonia in many animal species and humans. Globally, R. equi is most often recognized as causing severe pneumonia in foals that results in animal suffering and increased production costs for the many horse-breeding farms where the disease occurs. Because highly effective preventive measures for R. equi are lacking, thoracic ultrasonographic screening and antimicrobial chemotherapy of subclinically affected foals have been used for controlling this disease during the last 20 years. The resultant increase in antimicrobial use attributable to this “screen-and-treat” approach at farms where the disease is endemic has likely driven the emergence of multidrug-resistant (MDR) R. equi in foals and their environment. This review summarizes the factors that contributed to the development and spread of MDR R. equi, the molecular epidemiology of the emergence of MDR R. equi, the repercussions of MDR R. equi for veterinary and human medicine, and measures that might mitigate antimicrobial resistance at horse-breeding farms, such as alternative treatments to traditional antibiotics. Knowledge of the emergence and spread of MDR R. equi is of broad importance for understanding how antimicrobial use in domestic animals can impact the health of animals, their environment, and human beings.

Sign in / Sign up

Export Citation Format

Share Document