Background: Kaposis sarcoma-associated herpesvirus (KSHV or HHV-8) is the etiologic agent of Kaposis sarcoma (KS), multicentric Castlemans disease (MCD), and primary effusion lymphoma (PEL). KSHV is a nonubiquitous herpesvirus (~3% in the general US population) that can cause significant morbidity and mortality among immunocompromised hosts. However, routine surveillance of KSHV is lacking because diagnostic systems for viral identification are not of high enough sensitivity and specificity. This research describes a novel KSHV serological algorithm which increases sensitivity and specificity of KSHV detection beyond what has been previously reported.
Methods: A novel KSHV assay algorithm based on a baculovirus-expressed LANA1-GST fusion protein was used with previously described KSHV lytic antigen ELISAs. Initial assay evaluation was performed using 90 case sera from persons with AIDS- KS and 100 blood donor controls. We identified two multi-antigen algorithms: one that maximized sensitivity and one that maximized specificity. Sera from patients requiring bone-marrow transplantation, cadaveric renal transplant donors (CRTD), patients with systemic lupus erythematosus (SLE) and subjects with primary (PPH) and secondary pulmonary hypertension were obtained for KSHV testing.
Results: The highly sensitive algorithm yielded a sensitivity of 96% and a specificity of 94% and the highly specific algorithm a sensitivity of 93% and a specificity of 98%. Among CRTD, using the highly specific algorithm, overall seroprevalence was low at 4.0% (2/50) and similar to blood donors (P=0.46; OR=1.4; CI=0.14, 7.9). With the more specific algorithm, 8.0% (4/50) were infected compared to 6.4% (16/250) among blood donors (OR=1.3; CI=0.41,4.0; P=0.43). Among subjects requiring bone marrow transplantation seroprevalence was 3.0% and 10.0% and did not differ from blood donors (OR=2.0; 95% CI=0.10,122.9; P=0.50). Higher KSHV seroprevalence was observed among SLE patients using the specific algorithm (OR=6.0; 95% CI, 1.2-29.0) and the sensitive algorithm (OR=3.6; 95% CI, 1.1-12.2) though this is likely due to antigenic cross-reactivity as opposed to actual infection. Among patients with PPH we found no evidence of KSHV infection (0/19).
Conclusions: We used a systematic approach to standardize the assessment of KSHV infection rates and examined seroprevalence rates among high-risk populations of clinical interest. KSHV is of public health importance because it leads to cancer in immunocompromised hosts. Future studies of KSHV should focus on the cost-effectiveness of implementing surveillance systems such as the one described here, which could potentially lead to a marked reduction in KSHV-associated morbidity and mortality.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-12062005-084847 |
| Date | 03 February 2006 |
| Creators | Laney, Anthony Scott |
| Contributors | Lawrence Kingsley, DrPH, Clareann Bunker, PhD, Patrick Moore, MD, MPH, Lee Harrison, MD |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-12062005-084847/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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