Source: OKLAHOMA STATE UNIVERSITY submitted to NRP
A FIELD DEPLOYABLE RAPID ANAPLASMA DETECTION (RAD) KIT FOR SCREENING THREE ANAPLASMA SPECIES INFECTING LIVESTOCK
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
1015684
Grant No.
2018-67016-28311
Cumulative Award Amt.
$150,000.00
Proposal No.
2017-05718
Multistate No.
(N/A)
Project Start Date
Jun 15, 2018
Project End Date
Jun 14, 2021
Grant Year
2018
Program Code
[A1221]- Animal Health and Production and Animal Products: Animal Health and Disease
Recipient Organization
OKLAHOMA STATE UNIVERSITY
(N/A)
STILLWATER,OK 74078
Performing Department
Entomology and Plant Pathology
Non Technical Summary
This is a USDA-NIFA-AFRI Seed Award that focuses on detecting three major blood-borne diseases that affect cattle and sheep in the United States and around the world. The major disease of focus is Anaplasma marginale which causes bovine anaplasmosis, an economically important disease that annually impacts the cattle industry in the United States at estimates above $300 million. While short-term disease in cattle produces the largest loss in cattle numbers, cattle that survive the initial infection with Anaplasmosis will stay infected the rest of their lives. This chronic infection can pose a risk to the other cattle in the herd because these infections often 'wake up' in the infected cow and can be transmitted to other cattle through unsterile equipment (needles, knives), ticks or horse flies. Two other disease-causing bacteria, Anaplasma phagocytophilum and Anaplasma ovis, can also occur in livestock and could possibly affect humans as well. To date, there is a commercially available test provided by certified diagnostic veterinary laboratories to test cattle blood for bovine anaplasmosis. However, because of the shifting nature of Anaplasma infections in cattle, these tests don't always catch the infected cattle in a herd that are carrying the disease at a low level. There is a need to develop a simple, but effective screening test for producers that will provide rapid results at a low cost, yet be easy-to-use and accurate. To be the most helpful, this test should also be able to detect more than one species of Anaplasma. The goal of this project, then, is to develop a develop a specific and sensitive field deployable Rapid Anaplasma Detection (RAD) kit for the economical, large scale, and rapid screening of livestock (mainly cattle and sheep) for the detection of A. marginale, A. phagocytophilum and A. ovis. The project will have two main objectives. Objective One will put all the pieces together for a field-testing kit that will tell the difference between different types of Anaplasma using blood obtained from laboratory-infected animals. The second objective will take blood samples from cattle in sale barns across Oklahoma where Anaplasmosis occurs and make sure the kit works using fresh blood samples.
Animal Health Component
50%
Research Effort Categories
Basic
(N/A)
Applied
50%
Developmental
50%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
31133991170100%
Knowledge Area
311 - Animal Diseases;

Subject Of Investigation
3399 - Beef cattle, general/other;

Field Of Science
1170 - Epidemiology;
Goals / Objectives
Overall goal The overall goal of this research is to develop a specific and sensitive field deployable Rapid Anaplasma Detection (RAD) kit for the economical, large scale, and rapid screening of livestock (mainly cattle and sheep) for infection with Anaplasma marginale, A. phagocytophilum and A. ovis.Specific objectives Objective 1: To develop a RAD kit that will differentiate A. marginale, A. phagocytophilum, and A. ovis in cattle and sheep using defined blood isolates collected from cattle and sheep experimentally infected with regional strains of A. marginale and A. ovis, respectively, and cell culture stocks infected with A. phagocytophilum.Objective 2: To validate the RAD kit performance using blood samples collected from cattle in bovine anaplasmosis endemic areas of the U.S. and sheep in areas of the world where A. ovis is a problem.
Project Methods
Objective 1: To develop a RAD kit that will differentiate A. marginale, A. phagocytophilum, and A. ovis in cattle and sheep.The sample transport cartridge: An Elution-Independent Collection Device (EICD): The first component is a novel EICD for rapid (3-5 min) collection and sample preparation, and long-term storage at room temperature. Involving less time than the 15-30 minutes required using commercially available kits for sample preparation of microorganism's nucleic acid recovery, EICD is easy-to-operate, collects fluid specimens by contact and lateral flow filtration. This EICD will be an integral component of the RAD kit and will simplify the process of handling samples and assist operators who may not be familiar with DNA extractions for RPA or PCR assays.The DNA amplification assay: Replicase Polymerase Amplification (RPA) of DNA: RPA is a single tube, isothermal DNA amplification technology alternative to PCR. By adding a reverse transcriptase enzyme to an RPA reaction, it can detect RNA as well as DNA, without the need for a separate step to produce cDNA. Because it is isothermal, RPA reactions need much simpler equipment than PCR, which needs a thermal cycler. This ease of use and low-cost investment allows RPA technology to be used at local veterinary venues.Visualization component: We will use a rapid PCRD Nucleic acid lateral flow assay as an alternative to DNA agarose gel electrophoresis. PCRD is a rapid, safe and sensitive way to confirm the successful outcome of a DNA amplification exercise.Assay validation component: Artificial Positive Control (APC). The fourth technology refers to the development a safe APC, which will be multi-target, non-infectious and clonable for routine RPA and PCR-based assays.Objective 2: Validation of the RAD kit performance using blood samples collected from cattle and sheep. Once a functional assay capable of detecting varying parasitemias of the Anaplasma species in bovine and sheep blood is created, we will test it using blood samples from cattle at sale barns across Oklahoma and other Anaplasma endemic areas. We will also procure bovine and sheep blood samples where A. phagocytophilum and A. ovis is endemic. The final analysis will include a comprehensive analysis of sample costs, processing, and storage.

Progress 06/15/18 to 06/14/21

Outputs
Target Audience:The target audience of this research has been veterinary professionals and livestock producers in the United States and worldwide who are concerned with anaplasmosis infections in their herds. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This project has provided for the full-time training (course work as well as mentor-based training) of one graduate student in the areas of Animal Health, vector-borne disease transmission, and the development of multiplex diagnostics using blood products. Additionally, it has provided training for an undergraduate in the use and development of diagnostics for animal diseases. How have the results been disseminated to communities of interest?As already provided, the results from the study have been compiled into two manuscripts, one of which was just accepted for publication, and the other is in the review process. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? The overall goal of this research was to develop a specific and sensitive field-deployable Rapid Anaplasma Detection (RAD) kit for the economical, large-scale, and rapid screening of livestock (mainly cattle and sheep) for infection with Anaplasma marginale, A. phagocytophilum and A. ovis. In the last year of funding, the following has been accomplished in accord with our original plan: Objective 1: We have successfully completed the development of the RAD kit to differentiate A. marginale, A. phagocytophilum, and A. ovis in cattle and sheep using defined blood isolates collected from experimentally infected cattle (A. marginale) and sheep (A. ovis) and cell culture stocks infected with A. phagocytophilum. In this regard, we have 1) Optimized the RPA reaction using the Twistx kits, 2) Tested the specificity and sensitivity of our primers with known DNA samples; 3) Established protocols for the Elution Independent Collection Device for the collection of blood samples in the field that can be used directly in the RAD kit. 4) Successfully developed the artificial positive control. Objective 2: The collection of random samples from livestock auction centers in Oklahoma was completed. Extractions were completed for each sample and tests were run using the RPA primers in a PCR reaction as well as in the RAD kit. Additionally, we acquired A. marginale cELISA-positive samples from a diagnostic lab and ran them using the RPA-lateral flow assays.

Publications

  • Type: Journal Articles Status: Accepted Year Published: 2021 Citation: Salazar A, Ochoa-Corona FM, Talley JL, Noden BH. 2021. Recombinase polymerase amplification (RPA) with lateral flow detection for three Anaplasma species of importance to livestock health. Scientific Reports.


Progress 06/15/19 to 06/14/20

Outputs
Target Audience:The target audience of this research reached during this reporting period were cattle producers and veterinary professionals who focus on Anaplasma diseases within the United States. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? The funding has been used to cover the Graduate Research Assistantship for one Master's student: Ms. Andrea Salazar. Funding one undergraduate research assistants to help with various aspects of the project as needed. How have the results been disseminated to communities of interest?Two presentations have been given at professional meetings as a means to disseminate the results to interested communities. A poster was presented by PI Noden at the Conference of Research Workers in Animal Diseases (CWRAD) in Chicago (November 2019). The graduate student, Andrea Salazar, presented a poster of the work at the national meeting of the Entomological Society of America (ESA) in St. Louis (November 2019) and received the award for 1st Place Graduate Poster in the student competition What do you plan to do during the next reporting period to accomplish the goals?Under Goal 1 (To develop a RAD kit that will differentiate A. marginale, A. phagocytophilum, and A. ovis in cattle and sheep), we will complete the process of combining all the unique components of the RAD kit. Under Goal 2 (To validate the RAD kit performance using blood samples collected from cattle in bovine anaplasmosis endemic areas of the U.S), as per the proposal, we complete the testing the sensitivity and specificity of the developed RAD kit on random blood samples from over cattle from various areas of Oklahoma where Anaplasma is known to occur.

Impacts
What was accomplished under these goals? Under Goal 1: To develop a RAD kit that will differentiate A. marginale, A. phagocytophilum, and A. ovis in cattle and sheep. We have made considerable progress in the development of the RAD kit to differentiate A. marginale, A. phagocytophilum, and A. ovis in cattle and sheep. In accordance with our original timeline, we have successfully developed the pre-lysis treatment protocol for use in the field which includes the Elution Independent Collection Device for the collection of blood samples that can be applied directly in the RAD kit. We have assembled all of the proposed components of a fully-functional lateral flow RPA detection assay that serves as the basis for the RAD kit, complete with appropriate assay controls. All sensitivity and specificity testing has also been completed along with the development of artificial positive controls Under Goal 2: To validate the RAD kit performance using blood samples collected from cattle in bovine anaplasmosis endemic areas of the U.S. In accordance with our proposal, blood samples were obtained from random cattle from each of four sale barns in Oklahoma, representing 20 counties and 2 outside states. All samples have been tested by PCR and are in the process of being confirmed by the RAD assay. We are also in the process of working out some of the fine details involved with the field-application of the product.

Publications


    Progress 06/15/18 to 06/14/19

    Outputs
    Target Audience:The target audience of this research has been veterinary professionals and livestock producers in the United States and worldwide who are concerned with anaplasmosis infections in their herds Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This project has provided for the full-time training (course work as well as mentor-based training) of one graduate student in the areas of Animal Health, vector-borne disease transmission, and development of multiplex diagnostics using blood products. Additionally, it has provided training for an undergraduate in the use and development of diagnostics for animal diseases. How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals?By the next reporting period, the individual elements of the RAD device will be finalized and the RAD kit will be used to test blood obtained from cattle in Anaplasma-endemic areas of Oklahoma. Given the pace of the project to date, we feel that the goals of this project will be realized within the next year.

    Impacts
    What was accomplished under these goals? The overall goal of this research is to develop a specific and sensitive field deployable Rapid Anaplasma Detection (RAD) kit for the economical, large scale, and rapid screening of livestock (mainly cattle and sheep) for infection with Anaplasma marginale, A. phagocytophilum and A. ovis. In the last year of funding, the following has been accomplished in accord with our original plan: Objective 1: We have made significant progress in the development of the RAD kit to differentiate A. marginale, A. phagocytophilum, and A. ovis in cattle and sheep using defined blood isolates collected from cattle and sheep experimentally infected with regional strains of A. marginale and A. ovis, respectively, and cell culture stocks infected with A. phagocytophilum. In this regard, we have 1) Designed species-specific RPA primers from the msp4 gene that produce products of different sizes which can be incorporated into a multiplex lateral flow device; 2) Successfully isolated DNA from DMSO-stored blood samples and used it with our primers to differentiate species; 3) Optimized the RPA reaction using the Twistx kits, 4) Tested the specificity of our primers with known DNA samples; 5) Begun the process of working with the Elution Independent Collection Device for the collection of blood samples in the field that can be used directly in the RAD kit. Objective 2: The IACUC for the project was approved for the collection of blood from OK-based cattle in Anaplasma-endemic areas. Collection of samples has already begun and testing of these initial samples, using the primers in a PCR-reaction, was recently completed.

    Publications