The development of POC diagnostic technologies to detect Kaposi's sarcoma herpesvirus (KSHV or HHV8) in HIV-infected persons that utilizes oral or blood biospecimen technologies is of great clinical importance. Such technology would enable rapid POC diagnostic devices for the detection of KSHV infection, and referral for treatment for prevention and management of KSHV malignancies to prevent cancer- and AIDS-related mortality. In HIV/AIDS patients, coinfection with viruses such as KSHV, can lead to the development of Kaposi sarcoma (KS) tumors, which is the leading AIDS malignancy. KS frequently occurs in the oral cavity and KSHV is shed in saliva. KSHV also is the etiologic agent of primary effusion lymphoma (PEL) and is tightly linked with multicentric Castleman's disease, an aggessive lymphoproliferative disorder. Currently, there are no specific or highly effective treatment options for KS, PEL or multicentric Castleman's disease. KSHV transmission is currently poorly understood and most commonly occurs through saliva, where virus is shed at relatively high titers in the oral cavity. A better understanding of KSHV transmission would allow the development of strategies to disrupt KSHV transmission and prevent the risk of KSHV associated malignancies. Studies to enable better understanding of viral transmission will require frequent monitoring of KSHV shed in saliva. Second, KSHV viral load in blood has been shown to predict the onset of KS. In addition, KSHV viral load correlates with disease burden in KS patients and is lower during disease remission. Therefore, quantitative detection of KSHV is critical to optimal clinical management of those at risk for, and with, KSHV malignancy. The development of inexpensive, rapid detection of KSHV is therefore a priority. Our objective is to build a nanoplasmonic platform for the capture and detection of KSHV. Approaches will include detection of KSHV spiked in unstimulated whole saliva or blood samples and discarded, unstimulated whole saliva or blood patient specimens. Successful application of such an approach could lead to strategies for early detection of infection, cancer prevention, and monitoring of therapy. This platform technology is also widely applicable to other infectious agents including poxviruses, other herpesviruses, human papillomavirus (HPV), dengue, tuberculosis malaria, and Trichomonas vaginalis as well as early detection at the POC.

Public Health Relevance

The development of diagnostic technologies to detect KSHV in HIV-infected persons that utilizes biospecimen technologies is of great clinical importance to enable rapid POC diagnostic devices for the detection of disease and referral to treatment for prevention and management of KSHV malignancies, and therefore to prevent cancer- and AIDS-related mortality. Our objective is to build a nanoplasmonic platform for the capture and detection of KSHV spiked in unstimulated whole saliva or blood samples and discarded, unstimulated whole saliva or blood patient specimens for the early detection of KSHV infection, cancer prevention, and monitoring of therapy. This platform technology is also widely applicable to other infectious agents such as poxvirus, other herpesviruses, human papillomavirus (HPV), dengue, tuberculosis and malaria, and Trichomonas vaginalis at the POC.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE024971-04
Application #
9513508
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Gannot, Gallya
Project Start
2015-09-03
Project End
2020-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Stanford University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
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