Preventing HHV-8 transmission and Kaposi’s sarcoma (KS) risk prediction and prognostication in resource-poor countries

Background

Kaposi’s sarcoma (KS) is the now most important AIDS-defining malignancy in sub-Saharan Africa including Tanzania, and human herpesvirus-8 (HHV-8) is necessary for its development. Detecting HHV-8 in biopsies and its antibodies in sera allows the confirmation of KS diagnosis and predicts its risk among blood transfusion (BT) and organ transplant recipients but this is not yet routine in most African countries. This impedes the provision of safe BT/organ donation as well as KS prevention. A cost-effective HHV-8 serological assay for routine use will help improve blood/organ safety and lower iatrogenic KS incidence in resource-poor countries.

Materials and methods

Consecutive archival (1990-2001) biopsies and their corresponding sera from African patients with KS, non-KS tumors, and non-neoplastic (reactive) lesions at Muhimbili National Hospital (MNH) were evaluated by histopathology, immunohistochemistry (IHC) for the HHV-8 latency-associated nuclear antigen (LANA), and serology for HIV and HHV-8 (ELISA) as well as for HHV-8 [immunofluorescence (IFA)].

Results

A total of 184 biopsies and corresponding sera from 120 KS (65%), 24 non-KS tumors (13%), and 40 non-neoplastic lesions (22%) were evaluated. Most sera (89.0%, 164/184) were HHV-8+ by either IFA or ELISA (p<0.001, highly statistically significant, Chi² Test) and as expected the majority (68.3%, 112/164) were KS. HHV-8 serology tests by IFA and ELISA were mostly (92.4%, 73/79) concordant. 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. All patients with early-stage KS were HHV-8 seropositive but two late-stage cases were seronegative despite LANA expression in their corresponding biopsies.

Conclusions

HHV-8 frequency at MNH appears to be very high and necessitates routine screening of blood/organ donors and recipients to prevent viral transmission and lower risk of iatrogenic KS development. IFA and ELISA serology tests appeared highly concordant and ELISA showed higher PPV and specificity in detecting anti-HHV-8 antibodies. Thus ELISA might allow affordable HHV-8 screening in resource-poor countries like Tanzania, with most lacking the cell culture and fluorescence microscopy facilities needed in IFA. The apparent tissue (LANA)-serum HHV-8 antibodies discrepancy in late-stage KS suggests that serum HHV-8 might not be a good indicator of this tumor’s development.