Abstract
BackgroundThe association of the human herpesvirus-8/Kaposi's sarcoma (KS)-associated herpesvirus (HHV-8/KSHV) serology with various malignancies in Tanzania is not currently well established while previous studies were based on either PCR or immunofluorescence assays [IFA] but not with a sensitive enzyme-linked immunosorbent assay (ELISA). Selected archival diagnostic biopsies (n = 184) and sera from indigenous patients with KS (n = 120), non-KS tumors (n = 24) and non-neoplastic lesions (n = 40) at Muhimbili National Hospital (MNH), Tanzania, were evaluated by diagnostic histopathology, immunohistology [anti-HHV-8 latency-associated nuclear antigen (LANA)] and serology for HIV (ELISA) and HHV-8 (IFA and ELISA).ResultsAbout 66.3% (n = 122) cases including AIDS-associated Kaposi's sarcoma (AKS) (n = 93), reactive conditions (n = 28) and only one non-KS tumour were HIV positive. Endemic KS (EKS) patients were mostly males (96.3%, 26/27) who were less (69.9%, 65/93) predominant in AIDS-associated (AKS). A high (89%) percentage of patients with anti-HHV-8 antibodies was found in the cohort including the HIV positive (92%) cases, males (81.2%), KS patients (93%), non-KS tumors (92%), and reactive conditions (75%). All HHV-8 seronegative KS cases were nodular stage whereas both sera and corresponding biopsies from early stage KS were HHV-8+. Assay sensitivity, positive predictive value (PPV) and specificity were 98.6%, 93.5% and 16.7% for IFA and 93.5%, 98.6% and 50.0% for ELISA respectively.ConclusionHHV-8 seroprevalence at MNH appears high as expected among AKS cases and males but also in non-KS patients. ELISA showed a combination of high HHV-8 sensitivity as well as higher PPV and specificity than IFA which however, showed higher sensitivity. The apparent stage-dependent, inverted serum HHV-8 immunoreactivity supports a notion of viral immune-segregation during KS development. Routine HHV-8 screening should be considered particularly in patients at risk of KS and for selection of blood/organ donations.
Highlights
The association of the human herpesvirus-8/Kaposi's sarcoma (KS)-associated herpesvirus (HHV-8/Kaposi's sarcoma-associated herpes virus (KSHV)) serology with various malignancies in Tanzania is not currently well established while previous studies were based on either polymerase chain reaction (PCR) or immunofluorescence assays [IFA] but not with a sensitive enzyme-linked immunosorbent assay (ELISA)
The HIV and AIDS epidemic has dramatically increased the frequency of different malignancies Kaposi's sarcoma (KS) and certain malignant lymphoma (ML) which are associated with the novel human herpesvirus type 8 (HHV-8)/Kaposi's sarcoma-associated herpes virus (KSHV) and have become a major health concern in sub-Saharan Africa including Tanzania [1,2,3]
The tested non-KS Tanzanian sera in the previous study by Massambu et al, (2003) [6] were very few calling for the current larger study of hospital patients (KS, non-KS neoplasia and non-malignant clinical conditions), for comparison with our previous reports including that on healthy blood donors, which was based on immunofluorescence assay (IFA) and real-time PCR [5], The use of IFA necessitates culturing and subsequent processing of a HHV-8+ body cavity-based lymphoma (BCBL-1) cell line or another B-cell line (BCP-1) which may not be readily available and affordable in Tanzania on a routine/large scale screening basis
Summary
The association of the human herpesvirus-8/Kaposi's sarcoma (KS)-associated herpesvirus (HHV-8/KSHV) serology with various malignancies in Tanzania is not currently well established while previous studies were based on either PCR or immunofluorescence assays [IFA] but not with a sensitive enzyme-linked immunosorbent assay (ELISA). The tested non-KS Tanzanian sera in the previous study by Massambu et al, (2003) [6] were very few calling for the current larger study of hospital patients (KS, non-KS neoplasia and non-malignant clinical conditions), for comparison with our previous reports including that on healthy blood donors, which was based on immunofluorescence assay (IFA) and real-time PCR [5], The use of IFA necessitates culturing and subsequent processing of a HHV-8+ body cavity-based lymphoma (BCBL-1) cell line or another B-cell line (BCP-1) which may not be readily available and affordable in Tanzania on a routine/large scale screening basis. It is known that HIV transactivates HHV-8/ KSHV infection mostly by its Tat protein, the association of HHV-8 and HIV with non-KS neoplasia and non-malignant (reactive) conditions in Tanzania has not yet been examined and is evaluated in the present study [6]
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