Assay Sheet
Test ID
8000 HHV-8 Real-time qPCR
CPT Code
87799
Clinical Utility
HHV-8 is the etiologic agent of Kaposi’s Sarcoma (KS). Numerous studies have documented a higher risk of developing KS among HIV patients, organ transplant patients, and other immunocompromised individuals. Quantitative HHV-8 DNA PCR can be used to document the presence of the virus as well as track the course of infection.
Procedure
Extraction of HHV-8 viral DNA from blood, other biological fluids, or tissues followed by amplification and detection using real-time, quantitative PCR. An internal control is added to ensure the extraction was performed correctly and the PCR reaction was not inhibited. ViraCor’s assay design includes multiple targets to account for viral mutations, which exponentially reduces the chance of false negative results.
Specimens
Whole Blood: 3 to 5 ml collected in EDTA (lavender top) tube. Do not freeze; ship ambient.
Bone Marrow: 2 ml minimum, collected in an EDTA (lavender top) tube. Do not freeze; ship ambient.
Pleural Fluid: 1 ml submitted in a sterile, screw-top tube; ship ambient.
Tissue: Place in a sterile, screw-cap tube, add a small amount of saline to keep moist. Prefer 1 mm x 1 mm specimen. Prefer fresh over formalin fixed for maximum sensitivity; ship ambient.
Other specimens may be accepted for testing; however the following comment will appear in the final report: "The clinical utility of this result has not yet been demonstrated in the peer reviewed literature and is therefore unknown." Call ViraCor for further information.
Causes for Rejection
Whole blood frozen. Call ViraCor at 800-305-5198 if specimen is greater than 96 hrs old.
Specificity
The primers and probes used in this assay are specific for known strains of HHV-8 based on similarity search algorithms. Additionally, no cross reactivity was detected when tested against adenoviruses, BKV, CMV, EBV, HSV-1, HSV-2, HHV-6 variant A, HHV-6 variant B, HHV-7, JCV, parvovirus B19, SV-40, and VZV.
Human Herpes Virus-8 Assay Range
100 copies/ml to 1 x 1010 copies/ml
Turnaround Time
Same day (within 8 to 12 hours of receiving specimen), Monday through Saturday
Shipping
Ship Monday through Friday. Friday shipments must be labeled for Saturday delivery. All specimens must be labeled with patient's name and collection date. Multiple tests can be run on one specimen. Ship specimens FedEx Priority Overnight® to:
ViraCor Laboratories, 1001 NW Technology Dr, Lee's Summit, MO 64086
The CPT codes provided are based on ViraCor’s interpretation of the American Medical Association’s Current Procedural Terminology (CPT) codes and are provided for informational purposes only. CPT coding is the sole responsibility of the billing party. Questions regarding coding should be addressed to your local Medicare carrier. ViraCor assumes no responsibility for billing errors due to reliance on the CPT codes illustrated in this material. PCR tests are performed pursuant to a license agreement with Roche Molecular Systems, Inc. This assay was developed and the performance characteristics were determined at ViraCor Laboratories. This test is performed in a CLIA certified laboratory. FDA approval is not required for the performance of this test.
AS08-0808
Pathogen Overview
ABOUT HUMAN HERPES VIRUS-8
Human herpesvirus 8 (HHV-8), also known as Kaposi’s Sarcoma (KS) associated herpesvirus, is a member of the Herpesviridae family. It has a linear, double-stranded DNA genome with an icosahedral capsid. HHV-8 is a member of the Gammaherpesvirinae subfamily, along with EBV. HHV-8 is found only in humans. AIDS-related KS was first discovered in 1981; the association with HHV-8 was identified through DNA sequencing by Chang and colleagues in 1994. HHV-8 has subsequently been identified in all types of KS: classic, endemic, post-transplant, and AIDS-related KS; all of which have identical histological features. Research has shown a possible role for HHV-8 in the development of 2 rare lymphoproliferative disorders, multicentric Castleman’s disease (MCD) and primary effusion lymphoma (PEL).
In Europe and North America, the epidemiology of HHV-8 is very close to that of KS. HHV-8 antibodies are typically seen in individuals who have KS or are at high risk of developing it, such as homosexual men; but it is usually not found in low-risk individuals, such as general blood donors. HHV-8 infections in the general population are high in Africa, intermediate in Eastern Europe and the Mediterranean, and low in Europe and the United States.
Similar to other herpesviruses, HHV-8 establishes latency in the human host after a primary infection. The preponderance of evidence suggests that sexual contact, predominantly among homosexual men, is the principal route of transmission in Europe and North America, where it is rare to nonexistent in children. Recent prevalence data from Central Africa and the Mediterranean suggest a horizontal, nonsexual method of transmission among children in those regions.
HUMAN HERPES VIRUS-8 CLINICAL MANIFESTATIONS
Primary HHV-8 infection presents as a fever and rash. The fever typically lasts from 2 to 14 days, with the maculopapular rash persisting for 3 to 8 days.
HHV-8 reactivates in the form of KS, which was first identified in 1872 by Moriz Kaposi. It has since been characterized into 4 well-documented clinical variants:
- Classic KS primarily affects older males of Eastern European and Mediterranean lineage, and typically presents as cutaneous lesions on the lower extremities.
- Endemic KS occurs in Africa and may involve the lymph nodes in addition to typical skin lesions. This variant is often seen in children and HIV-negative individuals.
- Latrogenic KS occurs in recipients of solid organ transplants who are treated with immunosuppressive medications. This form of KS occurs more commonly in individuals of Mediterranean descent.
- AIDS KS is a very aggressive form first identified in the early 1980s in homosexual men who were otherwise healthy. In addition to cutaneous and lymphatic involvement, this variant often spreads to the lungs, GI tract, liver, and spleen. When AIDS KS was originally identified, the lifetime incidence was approximately 50% in homosexual men. As a result of antiviral therapy advances in the late 1990s, the incidence has declined markedly.
Transplant patients have a high risk of KS due to their level of immunosuppression. In renal transplant patients, the overall risk is in the range of 1 to 3%, with a median diagnosis interval of 29 to 31 months following transplant. One study of patients who were HHV-8 positive prior to renal transplant found that 23% of them developed KS, while only 0.7% of the seronegative controls developed KS. KS development post-transplantation has also been seen in heart and lung patients. HHV-8 infection has been noted as a cause of hematopoietic stem cell transplant (HSCT) failure. In these patients, the reactivated infection presents as fever with plasmacytosis, resulting in disseminated KS.
HUMAN HERPES VIRUS-8 LABORATORY DIAGNOSIS
Serology and molecular testing methods, such as polymerase chain reaction (PCR), are recommended. HHV-8 is not cultured in the clinical virology laboratory. Quantitative, real-time PCR allows for rapid, sensitive, and specific monitoring of the viral burden (viral load) in the patient, which allows the clinician to track the patient’s response to therapy.
HUMAN HERPES VIRUS-8 TREATMENT
While low dose cidofovir and high dose foscarnet or ganciclovir have been shown to suppress reactivation of HHV-8, they do not inhibit episomal virus DNA polymerase. This is suggestive of replication by host DNA polymerase with the latent form of the virus. Acyclovir has not been shown to be effective against HHV-8. Highly active retroviral therapy (HAART) has been shown to effectively reduce the incidence of AIDS KS.
Selected References
Ablashi DV, Chatlynne LG, Whitman JE, Cesarman E. Spectrum of Kaposi’s Sarcoma-associated herpesvirus, or human herpesvirus 8, diseases. Clin Microbiol Rev. 2002;(15):439-464.
Jenson HB. Human herpesvirus 8 infection. Curr Opin Ped. 2003;(15):85-91.
Knipe D, Howley P. Fields Virology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006.
Stebbing J, Portsmouth S, Gotch F, Gazzard B. Kaposi’s Sarcoma-an update. Int J STD AIDS. 2003;(14):225-227.
PAO-09-0707 PCR tests are performed pursuant to a license agreement with Roche Molecular Systems, Inc.
Abstracts & Publications
Ablashi DV, Chatlynne LG, Whitman JE, Cesarman E. Spectrum of kaposi's sarcoma-associated herpesvirus, or human herpesvirus 8, diseases. Clin Microbiol Rev. 2002;(15):439-464.
Most human herpesviruses are ubiquitous in most populations. They usually persist as long-term latent infections, and asymptomatic shedding of infectious virus is common. This shedding is responsible for horizontal primary transmission, usually from mother to child, so that initial infection occurs very early in life. Because they are so common, it has been very difficult to prove their role in the pathogenesis of malignant or nonmalignant diseases. An important exception to this rule, because of its limited and uneven distribution, is human herpesvirus 8 (HHV-8), also called Kaposi's sarcoma-associated herpesvirus (KSHV). In sub-Saharan Africa, antibodies to HHV-8 can be found in upwards of 30% of the general population. From 10 to 25% of people from the Mediterranean area are seropositive for the virus. Geographic pockets in this area with higher or lower seroprevalences can be found. In the rest of the world, the seroprevalence is low, 2 to 5%.
Jenson HB. Human herpesvirus 8 infection. Curr Opin Pediatr. 2003;(15):85-91.
Human herpesvirus 8, also known as Kaposi sarcoma-associated herpesvirus, is etiologically associated with Kaposi sarcoma and other rare malignancies. Human herpesvirus 8 infection is common in certain areas of Africa and Italy, but occurs in only 0% to 15% of adult populations in North America and Europe. Reports of human herpesvirus 8 prevalence of 3% to over 50% among children in Central Africa, Brazil, and South Texas suggest that horizontal transmission of human herpesvirus 8 occurs among children. Primary human herpesvirus 8 infection in immunocompetent children is associated with a fever and maculopapular rash.
Stebbing J, Portsmouth S, Gotch F, Gazzard B. Kaposi's sarcoma-an update. Int J STD AIDS. 2003;(14):225-227.
Although the incidence of Kaposi's sarcoma (KS) in established market economies has fallen since the introduction of highly active antiretroviral therapy (HAART), it remains the commonest tumour in individuals with human immunodeficiency virus infection. Kaposi's sarcoma-associated herpesvirus (KSHV) is the aetiologic agent of KS and its role in the subversion of cellular machinery has provided an understanding of fundamental mechanisms involved in immunobiology and Carcinogenesis. The continuous interactions between hosts and pathogens such as KSHV, during their coevolution have shaped the immune system and in turn, viruses have learned to manipulate host immune control mechanisms to facilitate their propagation. As viral proteins target many conserved pathways in cellular evolution, viral gene functions provide an insight into the mechanisms of cell biology and immunology. The virus must avoid apoptosis of cells to survive which in turn may lead to cellular proliferation and an increased risk of transformation.
