Epstein bar virus strains in peripheral blood and saliva Of mother-child pairs in malaria holoend~mic regions With varying burkitt's lymphoma incidence rates

Abstract

Endemic Burkitt's lymphoma is a polymicrobial childhood cancer disease mainly associated with EBV and plasmodium falciparum infections whose combined effects profoundly affect the B cell compartment. The exact role of these microbes in Burkitt's lymphoma pathogenesis as well as other EBV associated malignancies is not well understood. Genetic polymorphisms have led to the identification of:EJ3V type. 1 and 2 which may be specifically associated with some virus positive tumors. EBV strain prevalence and the effect of malaria infections on EBV specific immune T' cell responses in children at risk for BL in malaria holoendemic areas have not been studied. This study determined the prevalence of EBV type 1 and type 2, malaria infection prevalence and interferon gamma T cell responses in children and their mothers from BL 'hot' and 'cold' spots. Since EBV can be detected in both saliva and blood, this study compared the differences in virus types between these compartments as well. In a cross sectional study design, samples were collected from 58 Burkitt's lymphoma cold spot area participants and 37 Burkitt's lymphoma hot spot area participants. DNA was extracted. from peripheral blood and saliva and PCR amplification was done on all samples. PCR primers were used to amplify a region of the EBNA3C gene that can distinguish between the two strains based on the base pairs of the PCR product. EBV type 1 and 2 were identified based on length differences within the EBNA3C gene. Malaria infections were also determined by blood smears and compared with EBV infections and specific T cell responses from ELISPOT assays. EBVDNA was detected in 94.6% of the hot spot area samples and 86.2% of the cold spot area samples. 75.15% of the participants hadEBV in blood compared to 66.1% in saliva. EBV type 1 .and 2 multiple infections were detected in 94.6% of the hot spot area participants compared to 51.7% of the cold spot area participants. Single type 1 and type 2 EBV infections were detected at low frequencies in the cold spot area. Comparison of the type ofEBV found in mothers and children showed only 61.5% matchin blood and saliva all being typel and 2 multiple infections. In the cold spot area, 38.1% had matching strains in saliva and 57.1 in blood. 37.5% had type 1 single infections, 25% type 2 single infections, and 37.5% type 1 and 2 multiple infections in saliva. On the other hand, in the hot spot samples, 8.3% had type 1 single infections, 8.3% had type 2 single infections and 83.3% type 1 and 2 multiple infections. Chi-square analysis at P<0.05 showed significantly high detection of EBV DNA in the hot spot area samples compared to the cold spot area samples.' Type 1 and 2 co-infections were predominant in the hot spot blood and saliva samples. A high percentage of children from both study sites were co-infected with both EBV type 1 and 2. A high proportion of . mother-child pairs had matching EBV types in both blood and saliva compared to the hot spot (P< 0.05). Malaria infection prevalence was relatively high in the hot spot area compared to the cold spot area. EBV specific T cell responses were reduced in the malaria infected individuals compared to the uninfected individuals. Thisstudy concludes . . that EBV type 1 and 2 co-infections are highly prevalent in the malaria holoendemic region with high BL incidence rates and there is uniform EBV type transmission from the mothers to their children. EBV type distribution was not however dependent on the prevalence of malaria. EBV specific T cell immune responses tent to be suppressed by malaria infections.