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Summary Burkitt's lymphoma, an Epstein-Barr virus (EBV)-associated non-Hodgkin's malignant lymphoma is endemic in an area of Africa known as the Lymphoma Belt. This zone is demarcated by climatic requirements of temperature and rainfall. EBV-activating plant factors are among several co-factors which have been proposed for the development of epidemic Burkitt's Lymphoma (eBL). The distribution of Euphorbia tirucalli, a plant which possesses EBV-activating substances and can induce the characteristic 8:14 translocation of eBL in EBV-infected lymphoblastic cell lines in vitro, conforms closely to the climatic requirements of the Lymphoma. This plant, other EBV-activating plants and plants of unknown EBVactivating status with medicinal uses, are found significantly more often at the homes of eBL patients in Malawi than in those of controls.The possible role of these plant factors in the pathogenesis of eBL and their routes of bodily access are discussed. It is postulated that the associations described in this paper provide support for the theory that EBV-activating plants are co-factors involved in the pathogenesis of some cases of eBL.

The geographical and age distributions of endemic Burkitt's lymphoma (eBL), in Africa, parallel those of certain arboviruses, which include chikungunya fever. Increased incidences of antibodies to assorted arboviruses, including chikungunya, have been found in eBL sera compared to controls. An increased incidence and space-time case-clusters of eBL occurred during a chikungunya fever epidemic which were confirmed by serology and clinical observation. The present study, conducted in 1987-89, involved 108 eBL patients, and 97 local and 111 hospital controls. We examined, as hospital controls, patients with afebrile, non-malignant conditions admitted to Kamuzu Central Hospital, Malawi, during the eBL patients' first admission there. Analyses were for hospital controls and eBL patients at the end of their first admission and for local controls and eBL patients at the beginning of their third admission, about 8 weeks after the day of first admission, because of the local controls' temporal bias. Patients in case-clusters were among those seropositive for chikungunya virus, with a history compatible with arbovirus infection preceding the lymphoma, suggesting involvement of chikungunya virus in the case-clusters and a possible association between recent infection with this virus and development of the lymphoma. eBL patients were significantly more likely to be seropositive for chikungunya virus antibody (68x5%) than either hospital controls (46.8%) or local controls (50x5%) (P = 0x002 and 0x009, respectively), raising the possibility of an association between infection with an arbovirus and developing eBL in children already primed by holoendemic malaria and Epstein-Barr virus infection.

Certain infectious agents are associated with lymphomas, but the strength of the association varies geographically, suggesting that local environmental factors make important contributions to lymphomagenesis. Endemic Burkitt’s Lymphoma has well-defined environmental requirements making it particularly suitable for research into local environmental factors. The Epstein-Barr virus and holoendemic Malaria are recognized as important cofactors in endemic Burkitt’s Lymphoma and their contributions are discussed. Additionally, infection with Chikungunya Fever, a potentially oncogenic arbovirus, was associated with the onset of endemic Burkitt’s Lymphoma in one study and also with space-time case clusters of the lymphoma. Chikungunya Virus has several characteristics typical of oncogenic viruses. The Flavivirus, Hepatitis C, a Class 1 Human Carcinogen, closely related to the arboviruses, Yellow Fever, and Dengue, is also more distantly related to Chikungunya Virus. The mechanisms of oncogenesis believed to operate in Hepatitis C lymphomagenesis are discussed, as is their potential applicability to Chikungunya Virus.